P21 overexpressing immune cells with an antigen-binding domain at their surface

Abstract

The present invention concerns genetically modified immune cell, which (a) overexpresses p21 compared to a corresponding non-genetically modified immune cell, (b) expresses at its surface a recombinant antigen binding domain, and (c) is a monocyte, a macrophage, or a dendritic cell, as well as methods for producing them, pharmaceutical compositions comprising them, and their use as a medicament, in particular in the treatment of a subject suffering from a cell proliferative disorder, in particular cancer.

Description

[0001]P21 OVEREXPRESSING IMMUNE CELLS WITH AN ANTIGEN-BINDING DOMAIN AT THEIR SURFACE TECHNICAL FIELD OF THE INVENTION The present invention concerns a genetically modified immune cell, which (a) overexpresses p21 compared to a corresponding non-genetically modified immune cell, (b) expresses at its surface a recombinant antigen binding domain, and (c) is a monocyte, a macrophage, or a dendritic cell, as well as methods for producing them, pharmaceutical compositions comprising them, and their use as a medicament, in particular in the treatment of a subject suffering from a cell proliferative disorder, in particular cancer. BACKGROUND ART Cancer immunotherapy has demonstrated promising clinical results in the treatment of various solid tumors as well as in the treatment of hematologic tumors. Since the endogenous immune system is weakly reactive to malignant cells, in order to enhance the treatment of tumors it is necessary to force tumor recognition by the immune cells. This was achieved by genetic engineering of leukocytes. T cells were engineered to express a synthetic immunoreceptor comprising an extracellular targeted antibody and intracellular signaling domain. This receptor is called chimeric antigen receptor (CAR). Chimeric antigen receptor expressing macrophages were recently shown to support antigen- specific phagocytosis and to reduce tumor burden in preclinical mouse models of solid tumors expressing the human epidermal growth factor receptor 2 (HER2) (Klichinsky, M. et al., 2020; WO201719848). Programmed cell removal (PrCR) is a process of macrophage-mediated immune surveillance by which target cells are recognized and phagocytosed. Recently, it was demonstrated (international application WO2021 / 013764) that the cyclin-dependent kinase inhibitor CDKN1A (p21) acts as a negative transcriptional repressor of the phagocytosis inhibitory receptor SIRPα which is known to impair phagocytosis of cancer cells through its interaction with the “don’t eat me” signal CD47 (Veillette A. et al. 2018; Chao, M. P. et al., 2012) or independently to CD47 expression (Huang, C. et al.., 2024). Despite the obvious advantages of each one of these immunotherapies to treat various cancers a need still exists in the art for more effective therapies for treating cancers. The present invention responds to this need. SUMMARY OF THE INVENTION In the context of the present invention, the inventors surprisingly found that the adoptive transfer of genetically-engineered monocytes overexpressing p21 and expressing at their surface a chimeric antigen receptor (CAR) or cell binder (CB) specifically binding to an antigen of cancer cells into mouse preclinical cancer models led to their differentiation into phagocytosis-proficient tumor-associated macrophages (TAMs) that, after tumor cell engulfment, underwent proinflammatory activation and supported cancer regression. They further demonstrated that genetically-engineered monocytes combining p21 overexpression with an antigen binding domain (e.g., CAR or CB) displayed significantly improved cancer cell phagocytosis (and in particular polyphagocytosis) and proinflammatory activation after tumor phagocytosis than genetically-engineered monocytes with either p21 overexpression or the antigen binding domain such as a CAR or CB. Combining both approaches thus resulted in synergistic improvement of anticancer efficiency in several cancers, including cancers with bad prognosis such as triple-negative breast cancer (see Examples). In a first aspect, the present invention thus relates to a genetically modified immune cell, which: (a) overexpresses p21 compared to a corresponding non-genetically modified immune cell, (b) expresses at its surface a means for binding an antigen, preferably a recombinant antigen-binding domain, and (c) is a monocyte, a macrophage, a dendritic cell or a precursor of any of these cells. In some embodiments, the recombinant antigen-binding domain may be part of a fusion polypeptide further comprising a transmembrane domain. The present invention also relates to a vector, or a combination of two vectors, comprising: • a first polynucleotide encoding a recombinant antigen-binding domain, or a fusion polypeptide comprising the recombinant antigen-binding domain and a transmembrane domain, and • a second polynucleotide encoding a p21 protein. The present invention also relates to an in vitro method for producing a genetically modified immune cell according to the invention (e.g., a monocyte, macrophage, dendritic cell, or precursor of any of these cells) from a biological sample from a subject, comprising modifying the immune cell to overexpress p21 and to express at its surface a recombinant antigen-binding domain, sequentially or at the same time, for example: (a) transforming an immune cell or an immune cell population selected from monocytes, macrophages, dendritic cells and precursors of any of these cells from the biological sample, with: i. a first recombinant polynucleotide, or a first vector comprising a first recombinant polynucleotide, wherein the first recombinant polynucleotide encodes a recombinant antigen-binding domain as defined herein or a fusion polypeptide comprising a recombinant antigen-binding domain and a transmembrane domain as defined herein, and a second recombinant polynucleotide, or a second vector comprising a second recombinant polynucleotide, wherein the second recombinant polynucleotide encodes a p21 protein, or ii. a recombinant polynucleotide, or a vector comprising a recombinant polynucleotide, wherein the recombinant polynucleotide encodes (1) a recombinant antigen-binding domain as defined herein or a fusion polypeptide comprising a recombinant antigen-binding domain and a transmembrane domain as defined herein, and (2) a p21 protein. The present invention also relates to a pharmaceutical composition comprising: (a) the genetically modified immune cell according to the invention, or the vector, or combination of two vectors, according to the invention, and (b) a pharmaceutically acceptable excipient. The present invention also relates to use of such pharmaceutical composition comprising the vector or combination of two vectors, for example, for treating cancer, by administering to a subject: i. a first recombinant polynucleotide, or a first vector comprising a first recombinant polynucleotide, wherein the first recombinant polynucleotide encodes a recombinant antigen-binding domain as defined herein or a fusion polypeptide comprising a recombinant antigen-binding domain and a transmembrane domain as defined herein, and a second recombinant polynucleotide, or a second vector comprising a second recombinant polynucleotide, wherein the second recombinant polynucleotide encodes a p21 protein, or ii. a recombinant polynucleotide, or a vector comprising a recombinant polynucleotide, wherein the recombinant polynucleotide encodes (1) a recombinant antigen-binding domain as defined herein or a fusion polypeptide comprising a recombinant antigen-binding domain and a transmembrane domain as defined herein, and (2) a p21 protein. The present invention also relates to the genetically modified immune cell according to the invention, the vector or combination of two vectors according to the invention, or the pharmaceutical composition according to the invention, for use as a medicament. The present invention also relates to the genetically modified immune cell according to the invention, the vector or combination of two vectors according to the invention, or the pharmaceutical composition according to the invention, for use in the treatment of a subject suffering from a cell proliferative disorder, in particular a cancer. The present invention further relates to a method for treating a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the genetically modified immune cell according to the invention, the vector or combination of two vectors according to the invention, or the pharmaceutical composition according to the invention. DESCRIPTION OF THE FIGURES Figure 1. Characterization of p21-, CARHER2, p21-CARHER2 MDMs (a) Constructs used in lentiviral vectors to express p21 and / or CARHER2 (also designated HER2CAR) in MDMs. (b-e) p21 mRNA expression level in control (Co.TD) or p21- transduced (p21TD) MDMs (b), in Co.TD or CARHER2-transduced (CARHER2TD) (c), in Co.TD MDMs or in MDMs transduced with bicistronic lentiviral vectors for p21 and CARHER2 expression (p21-CARHER2TD) (d) and in Co.TD MDMs or in MDMs simultaneously transduced with 2 distinct lenviral vectors for p21 or CARHER2 expression (p21TD + CARHER2TD), respectively (e). Fold changes are shown. (f) SIRPα cell-surface expression of Co.TD, p21TD, CARHER2TD, p21-CARHER2TD and p21TD + CARHER2TD MDMs detected by flow cytometry at 15d after lentiviral transduction. (g, h) Binding of phycoerythrin (PE)- labeled recombinant HER2 on Co.TD, p21TD, CARHER2TD, p21-CARHER2TD and p21TD + CARHER2TD MDMs detected by flow cytometry at 15 d after lentiviral transduction. In (b- h), the data are presented as the mean±SEM from n=3 donors. *p<0.05, ***p<0.001 and ****p<0.0001 are determined with two-tailed ratio-paired t test (b-e) and one-way ANOVA with Tukey’s (f) or Dunnett’s multiple comparisons (g, h). Figure 2. Phagocytosis and polyphagocytosis of ovarian HER2+CD47+ SKOV3 cancer cells by MDMs overexpressing p21 and CARHER2 (a) Confocal micrograph of Co.TD and p21-CARHER2TD CMFDA+MDMs co-cultured with CMTMR+ SKOV3 cells. (b, c) Percentages of SKOV3 phagocytosis (b) and polyphagocytosis (c) by Co.TD, p21TD, CARHER2TD, p21-CARHER2TD and p21TD + CARHER2TD MDMs detected at indicated time of co-cultures. In (a), the data are representative of n=3 donors. In b and c the data are presented as the mean^SEM from n=3 donors. *p<0.05, ***p<0.001 and ****p<0.0001 are determined with one-way ANOVA with Tukey’s multiple comparison. Figure 3. Co-expression of p21 and CARHER2 enhances HER2-guided cancer cell removal in vitro (a) HER2 cell-surface expression of luciferase (Luc)-expressing ovarian SKOV3 (a), TNBC 4T1 (b) and breast TS / A (c) cancer cells detected by flow cytometry at basal level (a) or after HER2 overexpression (b, c). d-f Cell removal was evaluated by determining the luciferase activity of SKOV3 (d), 4T1 (e) and TS / A (f) cancer cells after 72-hour co- culture with Co.TD, p21TD, CARHER2TD, p21-CARHER2TD and p21TD + CARHER2TD MDMs. Percentages are shown. In a-f, the data are presented as the mean^SEM from n=3 donors. *p<0.05, ***p<0.001 and ****p<0.0001 are determined with two-tailed unpaired t test (a- c) and one-way ANOVA Tukey’s multiple comparison (d-f). Figure 4. Co-expression of p21 and CARHER2 enhances the proinflammatory activation of engineered MDMs Confocal micrographs (a) and percentages (b) of iNOS-expressing (iNOS+) MDMs detected after 72-hour co-culture of ovarian SKOV3 cancer cells with Co.TD, p21TD, CARHER2TD, p21-CARHER2TD and p21TD + CARHER2TD MDMs. In a, the data are representative of n=3 donors. In b, the data are presented as the mean^SEM from n=3 donors *p<0.05, ***p<0.001 and ****p<0.0001 are determined with one-way ANOVA with Tukey’s multiple comparisons test. Figure 5. Antitumor activity of adoptively-transferred, p21- and / or CARHER2 / p21-engineered human monocytes in xenograft model of ovarian cancer a Schematic representation showing the adoptive transfer of Co.TD, p21TD, and / or CARHER2TD or p21-CARHER2TD human Mos into SKOV3 tumor-bearing NSG mice (when tumor volumes reached 100 mm3). b, c Individual (b) or average (c) radiance curves of established SKOV3 tumors treated as indicated. d Kaplan-Meier survival curves of mice bearing established SKOV3 tumors, adoptively-transferred with Co.TD, p21TD, and / or CARHER2TD or p21-CARHER2TD human Mos. In (b), the data are individual tumor growth from n=10 mice / group. In (c-d), the data are presented as the mean^SEM from n=10 mice / group. *p<0.05, ***p<0.001 and ****p<0.0001 are determined with ordinary one-way ANOVA test (b,c) and log-rank Mantel-Cox test (d). Figure 6. Adoptively transferred p21-engineered monocytes (Mo) overexpressing chimeric antigen receptor (CAR) or cell binder (CB) against human epidermal growth factor receptor 2 (HER2) cure mice harboring ovarian cancer tumors. a Constructs used in lentiviral vectors to express p21, HER2CAR, and / or HER2CB in Mo. b, c Eight to ten weeks old female NOD.Cg-PrkdcscidIl2rgtm1Wjl / SzJ (NSG) immunodeficient mice (from Charles River) were intra-peritoneal injected with HER2+SKOV3-Luc cells (5x106cells / mouse). After 9 days, mice were surveyed and randomized for tumor growth determined by bioluminescence radiance (p / s / cm2) using IVIS spectrum in vivo imaging system. The control (Co.Mo), p21-engineered Mo (p21Mo), HER2CAR-engineered Mo (HER2CARMo), HER2CB-engineered Mo (HER2CBMo), HER2CAR / p21-engineered Mo (HER2CAR / p21Mo) and HER2CB / p21-engineered Mo (HER2CB / p21Mo) (5 x 106 / mouse) were suspended in 200 ^l DPBS and injected intravenously in the tail of mice bearing established HER2+SKOV3 tumors. Mice survival was then monitored. The ethical endpoints for mice sacrifice are the loss of 20% of body weight and / or clinical signs of illness. Individual (b) or average (c) radiance curves of established SKOV3 tumors treated as indicated. d Kaplan-Meier survival curves of mice bearing established HER2+SKOV3 tumors, adoptively-transferred with Co., p21, HER2CAR, HER2CB, HER2CAR / p21 or HER2CB / p21 Mo are shown. In (c), the data are presented as the mean^SEM from n=10 mice / group. Survival data are from n=10 mice / group. Statistical analysis was performed with GraphPad Prism 8.0 (GraphPad) and statistical significance (*p<0.05, **p<0.01, ***p<0.001 and ****p<0.0001) was determined with ordinary two-way ANOVA test (c) and log-rank Mantel-Cox test (d). Figure 7. Phagocytosis and polyphagocytosis of GD2+CD47+Hs578T TNBC cells by MDMs overexpressing p21, GD2CAR and / or GD2CB. a Constructs used in lentiviral vectors to express p21, GD2CAR, and / or GD2CB in Mo. b Percentages of MDMs overexpressing p21 after 7 days of differentiation of transduced Mo with control, p21, GD2CAR, HER2CB, HER2CAR / p21 or HER2CB / p21 lentiviruses. c, d Percentages of phagocytosis (c) and polyphagocytosis (d) of GD2+CD47+Hs578T TNBC cells by Co., p21, GD2CAR, GD2CB, GD2CAR / p21 or GD2CB / p21 MDMs detected at indicated time of co-cultures. In (b), (c) and (d), the data are presented as the mean^SEM from n=3 donors. *p<0.05, **p<0.01, ***p<0.001 and ****p<0.0001 are determined with two-way ANOVA with Tukey’s multiple comparison. Figure 8. Co-expression of p21 and GD2CAR or GD2CB enhances the proinflammatory activation of engineered phagocytic MDMs. a Percentages of iNOS-expressing (iNOS+) MDMs detected after 72-hour co-culture of GD2+CD47+Hs578T TNBC cells with Co., p21, GD2CAR, GD2CB, GD2CAR / p21 or GD2CB / p21 MDMs. In (a), the data are presented as the mean^SEM from n=3 donors *p<0.05, **p<0.01 and ****p<0.0001 are determined with two-way ANOVA with Tukey’s multiple comparisons test. Figure 9. Phagocytosis and polyphagocytosis of Nectin-4+CD47+MDA-MB468 TNBC cells by MDMs overexpressing p21, Nectin-4CAR and / or Nectin-4CB. a Constructs used in lentiviral vectors to express p21, Nectin-4CAR, and / or Nectin- 4CB in Mo. b Percentages of MDMs overexpressing p21 after 7 days of differentiation of transduced Mo with control, p21, Nectin-4CAR, Nectin-4CB, Nectin-4CAR / p21 or Nectin- 4CB / p21 lentiviruses. c, d Percentages of MDA-MB468 TNBC phagocytosis (c) and polyphagocytosis (d) by control, p21, Nectin-4CAR, Nectin-4CB, Nectin-4CAR / p21 or Nectin-4CB / p21 MDMs detected at indicated time of co-cultures. In (b), (c) and (d), the data are presented as the mean^SEM from n=3 donors. *p<0.05, **p<0.01, ***p<0.001 and ****p<0.0001 are determined with two-way ANOVA with Tukey’s multiple comparison. Figure 10. Co-expression of p21 and Nectin-4CAR or Nectin-4CB enhances the proinflammatory activation of engineered MDMs. a Percentages of iNOS-expressing (iNOS+) MDMs detected after 72-hour co-culture of MDA-MB468 TNBC cells with control, p21, Nectin-4CAR, Nectin-4CB, Nectin-4CAR / p21 or Nectin-4CB / p21 MDMs. In (a), the data are presented as the mean^SEM from n=3 donors **p<0.01, ***p<0.001 and ****p<0.0001 are determined with two-way ANOVA with Tukey’s multiple comparisons test. Figure 11. Phagocytosis, poly-phagocytosis and induced proinflammatory reprogramming of Claudin 18.2 (CLDN18.2)+CD47+SNU-601 human gastric cancer cells by MDMs overexpressing p21, CLDN18.2CAR and / or CLDN18.2CB. a Constructs used in lentiviral vectors to express p21, CLDN18.2CAR, and / or CLDN18.2CB in Mo. b Percentages of MDMs overexpressing p21 after 7 days of differentiation of transduced Mo with control, p21, CLDN18.2CAR, CLDN18.2CB, CLDN18.2CAR / p21 or CLDN18.2CB / p21 lentiviruses. c, d Percentages of phagocytosis (c) and poly-phagocytosis (d) of SNU-601 human gastric cancer cells by control, p21, CLDN18.2CAR, CLDN18.2CB, CLDN18.2CAR / p21 or CLDN18.2CB / p21 MDMs detected at indicated time of co-cultures. e Percentages of iNOS-expressing (iNOS+) MDMs detected after 72-hour co-culture of SNU-601 human gastric cancer cells with control, p21, CLDN18.2CAR, CLDN18.2CB, CLDN18.2CAR / p21 or CLDN18.2CB / p21 MDMs. In (b-e), the data are presented as the mean^SEM from n=3 donors. *p<0.1, **p<0.01, ***p<0.001 and ****p<0.0001 are determined with two-way ANOVA with Tukey’s multiple comparison test. DETAILED DESCRIPTION OF THE INVENTION Definitions A number of definitions are provided here that will assist in the understanding of the invention. However, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All references cited herein are incorporated by reference in their entirety. The singular forms “a” “an” and “the” are used in the sense that they include plural reference of the referenced components or steps, such as "at least one", "at least a first", "one or more" or "a plurality", unless the context clearly dictates otherwise. Thus, for example, a reference to "a cell" or "a microorganism" includes a plurality of cells or microorganisms, including mixtures thereof. The terms “comprise” “contain” “include” and variations thereof such as “comprising” are used herein in an inclusive sense, i.e., to specify the presence of the stated features but meaning that any further feature can be present in various embodiments of the invention. The terms "consist essentially of", "consist essentially in" and variations thereof such as "consisting essentially of" or "consisting essentially in" are used to specify the presence of the stated features but meaning that specific further feature that not materially affect the essential characteristics of the invention can be present in various embodiments of the invention. The terms "consist of", and variations thereof such as "consisting of" or "consisting in" are used in an exclusive sense, i.e., to specify the presence of the stated features meaning that no further feature can be present in various embodiments of the invention. As used herein, an “immune cell”, also referred to as a “white blood cell” or “leukocyte”, refers to a cell of the immune system. Immune cells notably comprise lymphocytes (B cells, T cells, and natural killer cells (also referred to as NK cells)), neutrophils, eosinophils, basophils, monocytes, macrophages and dendritic cells. The mononuclear phagocytic system (MPS) comprises peripheral blood circulating “monocytes”, their bone marrow or blood precursors and tissue-resident “macrophages” and “dendritic cells” (DCs). Besides their crucial role in tissue homeostasis, they are critically implicated in inflammation, autoimmunity, and cancer. Monocytes produce various substances, including prostaglandins, which are involved in inflammation and other physiological processes. They are also involved in engulfing and digesting cellular debris, pathogens such as bacteria and viruses, and dead cells through a process called phagocytosis. Monocytes originate from the bone marrow, where they develop from precursors known as monoblasts. Once released into the bloodstream, they circulate for about one to three days before migrating into tissues, where they differentiate into “monocyte-derived macrophages” (abbreviated as “MDM”) and “dendritic cells” (abbreviated as “DC”). Monocytes can be isolated from peripheral blood mononuclear cells (PBMC) by adherence to plastic in an appropriate medium (see examples). They are positive for the markers: CD14, CD11b and CD16 but negative for the markers CD56 (which is a marker of NK cells), CD3 (marker of T cells) and CD19 and CD20 (markers of B cells). MDM differentiated in the tissues are positive for the markers: CD14, CD11b, CD71, CD163 and CD206, but negative for the markers CD56 (which is a marker of NK cells), CD3 (marker of T cells) and CD19 and CD20 (markers of B cells). DCs are found in tissues that are in contact with the external environment, such as the skin, nose, lungs, stomach, and intestines. DCs are positive for the marker CD11c, but negative for the markers CD14 (marker of monocytes and MDM), CD56 (which is a marker of NK cells), CD3 (marker of T cells) and CD19 and CD20 (markers of B cells). As used herein, a “precursor” or a cell of interest relates to a cell that can differentiate under appropriate conditions into the cell of interest. A precursor does not need to be committed to the lineage of the cell of interest but only needs the ability to differentiate into the cell of interest when appropriate conditions for such differentiation are provided. Precursors of monocytes include Hematopoietic Stem Cells (abbreviated as “HSCs”, the earliest precursors that give rise to all blood cell lineages, including the myeloid lineage), Common Myeloid Progenitors (abbreviated as “CMPs”, which are derived from HSCs and can differentiate into various myeloid lineages), Granulocyte-Macrophage Precursors (abbreviated as “GMPs”, which arise from CMPs and are committed to producing granulocytes and monocytes), Macrophage-DC Precursors (abbreviated as “MDPs”, which are bipotent progenitors that can give rise to both monocytes and dendritic cells), monoblasts (the first committed progenitor cells in the monocyte lineage, they differentiate from MDPs and represent the initial stage of monocyte- macrophage maturation), and promonocytes (an intermediate stage between monoblasts and monocytes). Precursors of MDMs and DCs include all precursors of monocytes, as well as monocytes. “Hematopoietic stem cells” or “HSCs” are multipotent stem cells that give rise to all types of blood cell. Human HSCs can generally be identified based on their Lin- CD34+ CD38- CD45RA- CD90+ phenotype. “Common Myeloid Progenitors” or “CMPs” are derived from HSCs and can differentiate into various myeloid lineages and human CMPs can generally be identified based on their Lin- CD34+ CD38+ CD45RA- CD90- CD123int (i.e. IL-3R alpha int) phenotype. Human CMPs may be further CD117+ (i.e. c-Kit+) Flt3+ (i.e. CD135+) HLA-DR+. “Granulocyte-Macrophage Precursors” or “GMPs” arise from CMPs and are committed to producing granulocytes and monocytes. Human GMPs can generally be identified based on their Lin- CD34+ CD38+ CD45RA+ CD90- CD123+ (i.e. IL-3R alpha+) CD135+ phenotype. GMPs are generally further CD117+ (i.e. c-Kit+) FcγRII / III+ CD33+ HLA- DR+ CD4-. “Macrophage-DC Precursors” or “MDPs” are bipotent progenitors that can give rise to both monocytes and dendritic cells. Human MDPs can generally be identified based on their Lin- CD34+ CD38+ CD45RA+ CD90- CD123hi CD135+ CD117+ CD115+ (i.e. CSF1R +) phenotype. Human MDPS are generally also CD13+ CD33+ HLA-DR+. “Monoblasts” are the first committed progenitor cells in the monocyte lineage, they differentiate from MDPs and represent the initial stage of monocyte-macrophage maturation. Human monoblasts can generally be identified based on their CD34+ CD4low CD13+ CD33+ HLA-DR+ CD64- phenotype. “Promonocytes” are an intermediate stage between monoblasts and monocytes that can generally be identified based on their CD34- CD4+ CD11b+ CD13+ CD14 low CD33+ CD36+ CD64+ HLA-DR+ phenotype. By “amino acid”, it is referred to all the residues of the natural α–amino acid (for example alanine (Ala, A), arginine (Arg, R), asparagine (Asn, N), aspartic acid (Asp, D), cysteine (Cys), glutamine (Gln, Q), glutamic acid (Glu, E), glycine (Gly, G), histidine (His, H), isoleucine (Ile, I), leucine (Leu, L), lysine (Lys, K), methionine (Met, M), phenylalanine (Phe, F), proline (Pro, P), serine (Ser, S), threonine (Thr, T), tryptophan (Trp, W), tyrosine (Tyr, Y) and valine (Val, V) in the D or L form), as well as non-natural amino acids also referred to as amino acid analogs, such as citrulline (Cit), hydroxyproline (Hyp), hydroxylysine, norleucine (Nle), 3-nitrotyrosine, nitroarginine, ornithine (Orn), naphtylalanine (Nal), l’acide 2-aminobutanoïque (Abu), 2,4-diaminobutyric acid (DAB), methionine sulfoxide or methionine sulfone. The terms "peptide", "polypeptide" and "protein" are used interchangeably herein and refer to any polymer of covalently linked amino acids, regardless of length or post- translational modification. No limitation is placed on the maximum number of amino acids comprised in a polypeptide. As a general indication, the terms refer to both short polymers (typically designated in the art as peptide, or protein fragment) and longer polymers (typically designated in the art as polypeptide or protein). As a general indication and without being bound therein, if the amino acid polymer contains more than 50 amino acid residues, it is preferably referred to as a polypeptide or a protein, whereas if the polymer consists of 50 or fewer amino acids, it is preferably referred to as a "peptide". A polypeptide may be any translational product of a polynucleotide regardless of size. Alternatively, a polypeptide may be any product of a chemical synthesis reaction. The polypeptide can be linear, branched or cyclic, preferably linear. The polypeptide may comprise naturally occurring amino acids and / or amino acid analogues and it may be interrupted by non-amino acids. Amino acids in a polypeptide are typically covalently linked by peptide bonds. Preferably, all the chemical bonds in a polypeptide are peptide bonds. In some instances, the polypeptide may comprise one or more chemical bonds that are not peptide bonds. The term “polypeptide” encompasses native polypeptides as well as non-native polypeptides, including derivatives, mutated polypeptides, engineered polypeptides, fusion polypeptides, among others. The term “polypeptide” also encompasses polypeptide fragments and polypeptide multimers (e.g. dimers), including homo- and hetero-multimers. Polypeptides usable herein can be further modified by chemical or enzymatic modification. Such a chemically and / or enzymatically modified polypeptide comprises chemical groups other than the chemical groups of the 20 naturally occurring amino acids. Examples of such chemical or enzymatic modifications include post- translational modifications, addition of a label, etc. Chemical or enzymatic modifications of a polypeptide may alter one or more property(ies) of the polypeptide. For example, some modifications may alter stability, biological half-life, water solubility, activity, etc. The reading and writing senses of an amino acid sequence of a polypeptide as used herein are the conventional reading and writing senses. The reading and writing convention for amino acid sequences of a polypeptide places the amino terminus on the left, with the sequence then being written and read from the amino terminus (N-terminus) to the carboxyl terminus (C-terminus), from left to right. The term “fusion polypeptide” as used herein refers to a polypeptide comprising a first peptide linked (or conjugated, or bounded, or coupled, or attached) to a second peptide (i.e., one or more peptide(s) linked to one or more peptides). The terms “linkage”, “conjugation”, “bonding”, “coupling”, and “attaching” are herein used interchangeably. The first and second peptides (and optional other peptides included in the fusion polypeptide) are referred to as “fusion partners”. Linkage may involve terminal coupling, inside coupling, lateral coupling, and any combination thereof. Furthermore, a fusion polypeptide may comprise one or several linked peptides. Linkage may be covalent or not. Linkage may be chemical, enzymatic, or genetic, although genetic fusion is preferred. Linkage can be carried out by any acceptable means of bonding. In this regard, linkage can thus be performed by one or more covalent, ionic, hydrogen, hydrophobic or Van der Waals bonds, cleavable or non-cleavable in physiological medium or within cells. Furthermore, linkage can be performed at any reactive group(s) of the first polypeptide and / or the second peptide. When the fusion is a “genetic fusion”, the fusion is made through the covalent linkage in a single polypeptide chain (that can be linear or not (i.e. branched)) of the fusion partners and is performed by genetic means. In such case, linkage is made by fusing in frame the polynucleotides encoding each of the fusion partners. By "fused in frame", it is meant that the expression of the fused coding sequences results in a single polypeptide without any translational terminator between each of the fused polypeptides. Linkage may be direct or indirect (i.e., for the latter, via a linker). The fusion partners are said to be linked “directly” when there is no additional compound between the two fusion partners (the first and second peptides). For instance, in case of a genetic fusion, the polypeptide fusion partners are said to be linked directly when there is no additional amino acid residue between the two fusion partners (the first peptide and the second peptide). In contrast, the fusion partners are said to be linked “indirectly”, or “through a linker” when there is a compound referred to as a “linker” or “spacer” between the two fusion partners (the first and second peptides). Example of linkers include, but are not limited to, affinity based linkers (such as a linker derived from a couple biotin-streptavidin or from a couple antibody-antigen), covalent linkers (such as a –SH / -NH2 group, an amine maleimide NHS-ester (such as 3-(Maleimido)propionic acid N- hydroxysuccinimide ester), a compound targeting the c-terminal carboxyl group of a polypeptide (such as N-Hydroxysuccinimide), or a peptide (such as a peptide comprising 3 to 50 (random) amino acid residues). In case of indirect genetic fusion, the linker may be a peptide or a polypeptide, for example one comprising, or consisting essentially of, or consisting of, one or more amino acid residue(s). Such a peptide may be called a “peptide linker”. As used herein, a “peptide linker” or “peptide spacer” refers to a short sequence of amino acids used to connect two or more proteins or protein domains in a fusion protein. A peptide linker is generally added in order to provide flexibility between protein domains, allowing them to fold and function independently. A peptide linker is thus typically 1 to 30 amino acids long and is typically composed of small, hydrophilic amino acids like glycine, serine, threonine, asparagine, alanine and proline. Most commonly used peptide linkers comprise 2 to 15 amino acids and mainly comprise amino acids selected from glycine and serine, from glycine, serine and threonine, from glycine, serine, and alanine. The amino acid sequence of a peptide linker may further be designed to allow cleavage between the two fusion partners (the first and second peptides) by a specific protease. It is within the reach of the skilled person to assess the need to include or not a linker between the two fusion partners. The two fusion partners (the first and second peptides) may be fused in any order. “N-terminal fusion” or “N-terminal coupling” herein means that the second peptide is attached / linked / added / fused at the N-terminus of the first peptide, i.e. to the N- terminal amino acid residue of the first peptide. In contrast, “C-terminal fusion” or “C- terminal coupling” herein means that the second peptide is attached / linked / added / fused at the C-terminus of the first peptide, i.e. to the C-terminal amino acid residue of the first peptide). As used herein, the term “nucleotide” refers to any of various compounds consisting of a sugar, usually ribose or deoxyribose, a purine or pyrimidine base, and one or more (generally one, two or three) phosphates. The expression “nucleotide” designates both ribonucleotides (in which the sugar is a ribose) and deoxyribonucleotides (in which the sugar is a deoxyribose). It includes the naturally occurring ribonucleotide or deoxyribonucleotide monomers, and to related structural variants thereof, including derivatives and analogs, that are functionally equivalent with respect to the particular context in which the nucleotide is being used (e.g., hybridization to a complementary base: Adenine (A) pairs to Thymine (T) or Uridine (U) and Guanine (G) pairs to Cytosine (C)), unless the context clearly indicates otherwise. As used herein, the terms “polynucleotide” and “nucleic acid molecule” are used interchangeably and refer to a polymeric form of nucleotides of any length, including deoxyribonucleotides or ribonucleotides, or analogs thereof. A polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs, and may be interrupted by non-nucleotide components. If present, modifications to the nucleotide structure may be imparted before or after assembly of the polymer. The term polynucleotide includes both double-stranded and single-stranded molecules. Unless otherwise specified or required, any embodiment of the invention described herein that is a polynucleotide encompasses both the double-stranded form and each of two complementary single-stranded forms known or predicted to make up the double- stranded form. Unless otherwise specified, the terms "polynucleotide encoding a polypeptide" or “nucleic acid molecule encoding a polypeptide” or "nucleotide sequence encoding a polypeptide" are used interchangeably and include all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. As used herein, a “genetically modified cell” refers to a cell that has had its genome altered through the use of genetic engineering techniques. When referring to a cell, “genome” or “genetic material” refers to the entire set of nucleic acid instructions found in a cell. This term includes both chromosomes and extra-chromosomal nucleic acids. A “corresponding non-genetically modified cell” of a genetically modified cell refers to a cell which, except for the genetic alterations of its genome done by means of genetic engineering, is similar to the genetically modified cell. In other words, it should be understood that a genetically modified cell and a corresponding non-genetically modified cell originate from the same cell line or cell population, have preferably been cultured in similar cell culture conditions, and have preferably been submitted to a similar number of passages. Preferably, the genomes of the genetically modified cell and of the corresponding non-genetically modified cell differ only by the genetic alterations of its genome done by means of genetic engineering. In the context of the invention, “genetic engineering” includes, but is not limited to, PCR and DNA cloning technologies; transfection, transformation and other gene transfer technologies; homologous recombination; site-directed mutagenesis; and gene fusion. In the context of the invention, it should be understood that the cells are preferably genetically modified to express or overexpress polypeptides of interest. In the context of the invention, the terms “genetically modified to express” or “genetically modified to overexpress” a polypeptide of interest, when referring to a genetic modification of a cell should be construed as generally understood the art, that is to say that the alterations of the genetic material of the cell obtained through the use of genetic engineering techniques enable or increase the expression of the polypeptide of interest, compared to a cell that has not had its genetic material altered through the use of genetic engineering techniques. A polypeptide of interest may be a natural polypeptide, a fragment of a natural polypeptide, or a non-natural polypeptide such as a fusion polypeptide. A genetically modified cell, in particular when it is genetically modified to express or overexpress a polypeptide of interest, may notably express or overexpress a recombinant polynucleotide, which may encode the polypeptide of interest, which is then referred to as a recombinant polypeptide. As used herein, “recombinant”, when used in reference to a polynucleotide, means a polynucleotide that has been created through genetic recombination techniques, typically has been artificially manipulated or recombined, as opposed to occurring through natural processes. As used herein, “recombinant”, when used in reference to a polypeptide, means a polypeptide encoded by a recombinant polynucleotide. When a genetically modified cell expresses or overexpresses a recombinant polypeptide, the recombinant polypeptide may be endogenous or exogenous to the cell. As used herein, when referring to a recombinant polypeptide expressed or overexpressed in a genetically modified cell, “endogenous” means that the polypeptide is also naturally expressed by the genetically modified cell and its corresponding non- genetically modified cell. An endogenous polypeptide is thus expressed or overexpressed in addition to the natural expression of the same polypeptide naturally expressed by the corresponding non-genetically modified cell before genetic modification. A genetically modified cell will notably express an endogenous recombinant polypeptide when it has been transformed by a vector encoding a recombinant polypeptide that is the same as a polypeptide already naturally expressed by the cell before transformation. In contrast, when referring to a recombinant polypeptide expressed or overexpressed in a cell, “exogenous” means that a corresponding non-genetically modified cell does not naturally express the same polypeptide. This will notably be the case when a cell has been transformed by a vector encoding a recombinant polypeptide that is not naturally expressed by the cell before transformation. For instance, a recombinant polypeptide may not be naturally expressed by the cell before transformation because it is a non-natural polypeptide (such as a fusion polypeptide), because it is specifically expressed by another cell type, or because it is expressed by cells of another species. As used herein, an exogenous recombinant polypeptide may be allogenic or xenogenic. It will be referred to as “allogenic” when it is either naturally expressed by other cells from the same species (in particular by cells of another cell type but from the same species) or when it is a fusion polypeptide comprising fusion partners expressed by any cell of the same species. For instance, a monocyte transformed by a vector encoding a recombinant polypeptide naturally expressed by B lymphocytes (such as an antibody) of the same species or a fragment thereof (such as an ScFv) or a recombinant fusion polypeptide comprising fusions partners that are polypeptides of fragments thereof naturally expressed by cells of the same species will be a monocyte expressing an exogenous allogenic recombinant polypeptide. In contrast, an exogenous recombinant polypeptide will be referred to as “xenogenic” when the recombinant polypeptide or at least one fusion partner it comprises when it is a fusion polypeptide is naturally expressed by cells of another species. As used herein, “overexpress” refers to an increased level of expression of an expression product, such as an mRNA or a polypeptide, compared to a level of reference. Preferably, in the context of the invention the term “overexpress” refers to stable overexpression of the expression product, such as an mRNA or a polypeptide, compared to a level of reference. Preferably, in the context of the invention, the term “overexpress” refers to an increased level of a polypeptide of interest, compared to the expression level of said polypeptide in reference conditions. The expression level of a polypeptide can be detected by any conventional means enabling the measurement of polypeptide levels, such as Western blot. Methods and means to increase the expression level of a polypeptide in a cell are well known to one of ordinary skill in the biotechnology and genetic engineering field, and include stimulation of the natural expression of an endogenous polypeptide by culturing the cell in a medium comprising a compound able to stimulate the expression of the endogenous polypeptide or altering the regulatory sequences of the endogenous gene (e.g. mutating or changing the endogenous promoter, adding an enhancer, etc.), but also gene editing or transformation of the cell by a vector expressing the polypeptide of interest. In the case of a cell that has been genetically modified to overexpress a polypeptide of interest, the level of reference is preferably the expression level of the polypeptide of interest in a corresponding non-genetically modified cell. In the context of the invention, the phrase “overexpresses p21 compared to a corresponding non-genetically modified immune cell” refer to cells which exhibit overall increased expression level of p21 compared to the overall expression level of p21 in corresponding non-genetically modified immune cell. In other terms, the level of the p21 protein is higher in the genetically modified immune cell of the invention than in corresponding non-genetically modified immune cell. This overexpression can be detected by any conventional means enabling the measurement of polypeptide levels, such as Western blot. In the context of the invention, the terms “is modified to overexpress p21” refer to any modification made to the immune cell using biotechnological tools and leading to transient or stable overexpression of p21. When referring to a polypeptide of interest, the terms “increased expression” refer to a level of expression of the polypeptide of interest that is equal to at least 1.2, 1.3, 1.4; 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 15, 20, 2530, 40, 50, 60, 70, 80, 90, 100, 500, 1,000, 5,000, 10,000-fold a reference value. As used herein, “underexpress” refers to a decreased level of expression of an expression product, such as an mRNA or a polypeptide, compared to a level of reference. Preferably, in the context of the invention the term “underexpress” refers to stable underexpression of the expression product, such as an mRNA or a polypeptide, compared to a level of reference. Preferably, in the context of the invention, the term “underexpress” refers to a decreased level of a polypeptide of interest, compared to the expression level of said polypeptide in reference conditions. The expression level of a polypeptide can be detected by any conventional means enabling the measurement of polypeptide levels, such as Western blot. Methods and means to decrease the expression level of a polypeptide in a cell are well known to one of ordinary skill in the biotechnology and genetic engineering field and include inhibiting of the natural expression of an endogenous polypeptide by culturing the cell in a medium comprising a compound able to inhibit the expression of the endogenous polypeptide or altering the regulatory sequences of the endogenous gene (e.g. mutating or changing the endogenous promoter, deleting an enhancer, etc.), but also knock out of the gene in the cell. In the case of a cell that has been genetically modified to underexpress a polypeptide of interest, the level of reference is preferably the expression level of the polypeptide of interest in a corresponding non-genetically modified cell. In the context of the invention, the phrase “underexpresses SIRP-alpha compared to a corresponding non-genetically modified immune cell” refer to cells which exhibit decreased expression level of SIRP-alpha compared to the expression level of SIRP-alpha in corresponding non-genetically modified immune cell. In other terms, the level of the SIRP-alpha protein is lower in the genetically modified immune cell of the invention than in corresponding non-genetically modified immune cell. This underexpression can be detected by any conventional means enabling the measurement of polypeptide levels, such as western blot. When referring to a polypeptide of interest, the terms “decreased expression” refer to a level of expression of the polypeptide of interest that is equal to at most 0.8, 0.7, 0.6, 0.6, 0.4, 0.3, 0.2, 0.1, 0.075, 0.05, 0.025, 0.01, 0.0075, 0.005, 0.0025, 0.001, 0.00075, 0.0005, 0.00025, 0.0001, 0.000075, 0.00005, 0.000025, 0.00001-fold a reference value. As used herein, the term “p21” or “p21 protein” designates interchangeably the cyclin-dependent kinase inhibitor 1 which is also known as “p21Cip1”, “p21Waf1”, “Waf1”, “CDKN1A”, “CAP20”, “CIP1”, “MDA-6”, “SDI1” and “CDK-interacting protein 1”. This protein binds to and inhibits the activity of the cyclin-CDK1, CDK2 and CDK4 / 6 complexes and thus functions as a regulator of cell cycle progression at G1 and S phase. The binding of p21 to CDK complexes occurs through p21’s N-terminal domain, which is homologous to the other CIP / CDK inhibitors p27 and p57. As a major target of p53 activity, it is usually associated with linking DNA damage to cell cycle arrest. This protein is encoded by the CDKN1A gene (Entrez Gene ID: 1026) of SEQ ID NO: 1 (Genbank accession number NM_078467) located on the chromosome 6 (6p21.2) in humans. In mice, the protein is encoded by the CDKN1A gene of SEQ ID NO: 3 (Genbank accession number NM_007669). The human p21 protein has the amino acid sequence of SEQ ID NO: 2 (Genbank accession number NP_000380), whereas the mouse p21 protein has the amino acid sequence of SEQ ID NO: 4 (Genbank accession number NP_031695). The terms “p21 protein” herein also encompass functional variants and / or fragments of the above-mentioned p21 proteins. “Functional variants of a p21 protein” are for example the wild-type p21 proteins of animal species other than human or mouse (e.g., from horse, dog, cats, or cattle animals). These proteins are now well-characterized and their sequence can be easily retrieved from conventional data bases. “Functional variants” are also mutated version of the natural p21 proteins, that comprise an amino acid sequence sharing a percentage of identity of at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% with the wild-type protein of the corresponding species (for a human therapy, with SEQ ID NO: 2, for a mouse therapy, with SEQ ID NO: 4, etc). Functional variants retain p21 activity, in particular p21 activity to enhance the programmed cell removal (PrCR) of tumor cells by macrophages. “Functional fragments of a p21 protein” are any fragment of the wild-type p21 protein or of functional variants thereof, that retains the activity of p21 protein, in particular p21 activity to enhance the programmed cell removal (PrCR) of tumor cells by macrophages. In some embodiments, the p21 activity is measured by measuring underexpression of SIRP-alpha. As used herein, the terms “signal regulatory protein alpha” or “SIRP-alpha” or “SIRPA” are used interchangeably and designate the signal regulatory protein alpha, which is also known as “BIT”; “MFR”; “P84”; “SIRP”; “MYD-1”; “SHPS1”; “CD172A”; “PTPNS1”. This protein is a member of the signal-regulatory-protein (SIRP) family, and also belongs to the immunoglobulin superfamily. SIRP family members are receptor-type transmembrane glycoproteins known to be involved in the negative regulation of receptor tyrosine kinase-coupled signaling processes. This protein can be phosphorylated by tyrosine kinases. This protein was found to participate in signal transduction mediated by various growth factor receptors. CD47 has been demonstrated to be a ligand for this receptor protein. This protein is encoded by the SIRPA gene (Entrez Gene ID: 140885) located on the chromosome 20 (20p13) in humans. Several isoforms of the human SIRP- alpha protein are known. Their amino acid and nucleotide sequences are presented in Table 1 below: Description Amino acid sequence Nucleotide sequence (Genbank accession (Genbank accession number) number) Synthetic construct Homo sapiens AIC61336.1 KJ903815.1 clone ccsbBroadEn_13209 SIRPA gene, encodes complete protein isoform 1 precursor variant (1) NP_001035111.1 NM_001040022.1 isoform 1 precursor variant (2) NP_001035112.1 NM_001040023.2 isoform 1 precursor variant (3) NP_542970.1 NM_080792.3 isoform 2 precursor variant (4) NP_001317657.1 NM_001330728.1 GRCh38.p14 Primary Assembly, XP_047295873.1 XM_047439917.1 isoform X4 GRCh38.p14 Primary Assembly, XP_047295875.1 XM_047439919.1 isoform X5 GRCh38.p14 Primary Assembly, XP_005260727.1 XM_005260670.4 isoform X1 GRCh38.p14 Primary Assembly, XP_024307604.1 XM_024451836.2 isoform X1 GRCh38.p14 Primary Assembly, XP_047295872.1 XM_047439916.1 isoform X3 GRCh38.p14 Primary Assembly, XP_047295874.1 XM_047439918.1 isoform X4 GRCh38.p14 Primary Assembly, XP_047295876.1 XM_047439920.1 isoform X5 GRCh38.p14 Primary Assembly, XP_047295871.1 XM_047439915.1 isoform X2 GRCh38.p14 Primary Assembly, XP_011527475.1 XM_011529173.3 isoform X2 Alternate T2T-CHM13v2.0, isoform XP_054179026.1 XM_054323051.1 X4 Alternate T2T-CHM13v2.0, isoform XP_054179028.1 XM_054323053.1 X5 Alternate T2T-CHM13v2.0, isoform XP_054179022.1 XM_054323047.1 X1 Alternate T2T-CHM13v2.0, isoform XP_054179027.1 XM_054323052.1 X4 Alternate T2T-CHM13v2.0, isoform XP_054179023.1 XM_054323048.1 X1 Alternate T2T-CHM13v2.0, isoform XP_054179025.1 XM_054323050.1 X3 Alternate T2T-CHM13v2.0, isoform XP_054179029.1 XM_054323054.1 X5 Alternate T2T-CHM13v2.0, isoform XP_054179024.1 XM_054323049.1 X2 Table 1. Isoforms of the human SIRP-alpha protein and their amino acid and nucleotide sequences. In the context of the present invention, SIRPA may designate any of the above described isoforms, or a functional variant or a functional variant thereof. The term “SIRP-alpha” herein also encompass functional variants and / or fragments of the above-mentioned SIRP-alpha protein. “Functional variants of a SIRP-alpha protein” are for example the wild-type SIRP- alpha proteins of animal species other than human (e.g., from mouse, horse, dog, cats, or cattle animals). These proteins are now well-characterized and their sequence can be easily retrieved from conventional data bases. “Functional variants” are also mutated version of the natural SIRP-alpha protein, whose amino acid sequence share a percentage of identity of at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% with the wild-type protein of the corresponding species. Functional variants retain SIRP-alpha activity, in particular SIRP-alpha activity to inhibit the programmed cell removal (PrCR) of tumor cells by macrophages. “Functional fragments of a SIRP-alpha protein” are any fragment of the wild-type SIRP-alpha protein or of functional variants thereof, that retains the activity of SIRP-alpha protein, in particular SIRP-alpha activity to inhibit the programmed cell removal (PrCR) of tumor cells by macrophages. The percent identities referred to in the context of the disclosure of the present invention are determined based on an optimal global alignment of the sequences to be compared taken in their entirety over their entire length, which may therefore comprise one or more insertions, deletions, truncations and / or substitutions. This percent identity may be calculated by any sequence analysis method well-known to the person skilled in the art. In addition to manual comparison, it is possible to determine global alignment using the algorithm of Needleman and Wunsch (1970). For nucleotide sequences, the sequence comparison may be performed using any software well–known to a person skilled in the art, such as the Needle software. The parameters used may notably be the following: “Gap open” equal to 10.0, “Gap extend” equal to 0.5, and the DNAFULL matrix (NCBI EMBOSS Version NUC4.4). For amino acid sequences, the sequence comparison may be performed using any software well–known to a person skilled in the art, such as the Needle software. The parameters used may notably be the following: “Gap open” equal to 10.0, “Gap extend” equal to 0.5, and the BLOSUM62 matrix. All Genbank accession number references correspond to those of Genbank release 261 of June 15, 2024. As used herein the term "antigen" refers to a substance, which is capable of being recognised (typically via its epitope(s)) by the immune system, preferably by the adaptive immune system, and which is capable of eliciting an antigen-specific immune response, e.g., by formation of antibodies and / or antigen-specific T cells as part of an adaptive immune response. An antigen may be a polypeptide, carbohydrate, nucleic acid, lipid, hapten or other naturally occurring or synthetic compound. Typically, an antigen may be or may comprise a peptide or protein, which may be presented to (antigen-specific) T- cells on the surface of Major histocompatibility complex (MHC) molecules by antigen- presenting cells. Antigens are usually peptides, proteins, sugars (such as polysaccharides or polyosides) and their lipid derivatives (lipids). Antigens can also be nucleic acids, or haptens (i.e. fragments of antigens). In the context of the invention, antigens include, but not limited to, biological components (e.g. peptides, polypeptides, post translational modified polypeptides and polynucleotides); complex components (e.g. cells, cell mixtures, live or inactivated organisms such as bacteria, viruses, fungi, prions, etc...), and combinations thereof. As used herein, an “antigen-binding domain” or “ABD” refers to a portion of a polypeptide that specifically binds to an antigen, which portion comprises the amino acid residues of the polypeptide that interact with the antigen and confer to the polypeptide its specificity and affinity for the antigen. Antigen binding domains notably include ligand- binding domain (such as ligand binding domains found in receptors and EF Hand binding domains) and immunoglobulin-like antigen-binding domains such as those found in antibodies or antibody fragments or antibody derivatives. As used herein, “antibody” or “immunoglobulin” is meant a molecule comprising a binding domain (i.e. at least one binding domain) for a given antigen and a constant domain comprising an Fc fragment capable of binding to Fc receptors (FcR). In most mammals, like humans and mice, an antibody consists of four polypeptide chains: two heavy chains and two light chains bound together by a variable number of disulfide bridges providing flexibility to the molecule. Each light chain consists of a constant domain (“CL”) and a variable domain (“VL”); the heavy chains consisting of a variable domain (“VH”) and three or four constant domains (CH1 to CH3 or CH1 to CH4) according to the isotype of the antibody. However, camelids (such as alpaca, llama, camel, vicuna and guanaco) produce antibodies that consist of only two heavy chains (no light chain is present), each heavy chain comprising a variable domain (referred to as “VHH”) and a constant region without a CH1 domain. Similarly, antibodies of cartilaginous fishes (such as sharks, rays, chimeras, and skates) produce antibodies referred to as immunoglobulin new antigen receptor (IgNAR), which also consist of only two heavy chains (no light chain is present). The two heavy chains comprise a variable domain (referred to as “VNAR”) and five constant domains and dimerize via the five constant domains, while the two variable domains (VNARs) are unpaired, forming the tips of the IgNARs (Roux et al., 1998; Diaz et al., 2002; Zielonka et al., 2015). The variable domains are involved in antigen recognition, while the constant domains are involved in the biological, pharmacokinetic and effector properties of the antibody. The variable domain differs from one antibody to another. Indeed, the genes encoding antibody heavy and light chains are respectively generated by recombination of three and two distinct gene segments called VH, DH and JH–CH for the heavy chain and VL and JL–CL for the light chain. The CH and CL segments do not participate in recombination and form the constant regions of the heavy and light chains, respectively. Recombinations of the VH–DH–JH and VL–JL segments form the variable regions of the heavy and light chains, respectively. The VH and VL regions each have three hypervariable zones or complementarity–determining regions (CDRs) called CDR1, CDR2 and CDR3, with CDR3 being the most variable since it is located in the recombination zone. These three CDRs, and particularly CDR3, are found in the portion of the antibody that will be in contact with the antigen and are thus very important for antigen recognition. Thus, antibodies retaining the three CDRs and each of the heavy and light chains of an antibody mostly retain the antigen specificity of the original antibody. In a certain number of cases, an antibody retaining only one of the CDRs, and notably CDR3, also retains the specificity of the original antibody. CDR1, CDR2 and CDR3 are each preceded by FR1, FR2 and FR3, respectively, corresponding to framework regions (FRs) that vary the least from one VH or VL segment to another. CDR3 is also followed by a framework region, FR4. An antibody’s CDRs are defined by the amino acid sequence of its heavy and light chains compared to criteria known to a person skilled in the art. Various methods for determining CDRs have been proposed, and the portion of the amino acid sequence of a heavy or light chain variable region of an antibody defined as a CDR varies according to the method chosen. The first determination method is that proposed by Kabat et al. (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991)). In this method, CDRs are defined by looking for the amino acids responsible for antibody–antigen binding. A second method was proposed by the IMGT, based on determining hypervariable regions. In this method, a unique numbering has been defined to compare variable regions regardless of the antigen receptor, chain type or species (Lefranc, M.–P. et al. Dev. Comp. Immunol., 27, 55–77 (2003)). This numbering provides a standardized definition of framework regions ((FR1–IMGT: positions 1 to 26, FR2–IMGT: 39 to 55, FR3–IMGT: 66 to 104 and FR4–IMGT: 118 to 128) and complementarity–determining regions (CDR1–IMGT: positions 27 to 38, CDR2–IMGT: positions 56 to 65 and CDR3–IMGT: positions 105 to 117). Finally, there is also a numbering called “common” in which the sequence of a particular CDR corresponds to the common sequence between the Kabat numbering and the IMGT numbering. Throughout the present description, the CDR sequences are indicated by the IMGT numbering. In particular, the CDRs have been determined by using the IMGT / V–QUEST program available at http: / / www.imgt.org / IMGT_vquest / share / textes / and described in Brochet et al.–2008 (Brochet, X. et al. Nucl. Acids Res. 36, W503–508 (2008)). Unlike the variable domains, whose sequence strongly varies from one antibody to another, the constant domains are characterized by an amino acid sequence that is very similar from one antibody to another, typical of the species and the isotype, with optionally a few somatic mutations. The Fc fragment naturally consists of the heavy chain constant region excluding the CH1 domain, i.e., the lower hinge region and the constant domains CH2 and CH3 or CH2 to CH4 (depending on the isotype). In human IgG1, the complete Fc fragment consists of the C–terminal portion of the heavy chain starting from the cysteine residue at position 226 (C226), the numbering of amino acid residues in the Fc fragment being throughout the present description that of the EU index described in Edelman et al.–1969 (Edelman, G.M. et al., Proc. Natl. Acad. USA, 63, 78–85 (1969)) and Kabat et al.–1991 (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991)). The corresponding Fc fragments of other types of immunoglobulins may easily be identified by a person skilled in the art by sequence alignments. As used herein, antibodies include antibodies of any species, including but not limited to mammalian antibodies (such as murine antibodies, hamster antibodies, goat antibodies, rabbit antibodies, human antibodies, and camelid antibodies) and cartilaginous fishes’ antibodies (such as shark antibodies), and also chimeric antibodies (including humanized antibodies). Antibodies as defined herein can be raised against any type of antigen. The antibodies can be of any isotype (e.g., IgG, IgE, IgM, IgD, IgA and IgY), any class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2), or any subclass (e.g., IgG2a, IgG2b, IgNAR) of immunoglobulin molecule. By “antibody fragment”, it is herein referred to a functional fragment of an antibody, which retains at least one function of the parental antibody from which it has been obtained. Antibody fragments notably include antigen-binding antibody fragments, which retain the ability of the parental antibody to specifically bind to its antigen. An antigen-binding antibody fragment typically comprises at least part of the variable region(s) of the parental antibody, in particular the CDRs and most particularly the CDR3 of each chain. Examples of antigen-binding antibody fragments include but are not limited to Fv, Fab, Fab’, F(ab’)2, and nanobody fragments. “Fv fragment” or “variable fragment” refers to an antibody fragment formed by non-covalently associated VH and VL domains of antibodies comprising two heavy chains and two light chains. A “Fab fragment” refers to a fragment formed by the assembly of the part of the heavy chain located upstream of the papain cleavage site (the CH1 domain is included, but not the hinge region or the other CH domains) and the whole light chain of an antibody of interest comprising two heavy chains and two light chains. The 2 chains are linked by a disulfide bridge, as in whole Ig. Fab fragments are monomers of around 50 kDa. A “Fab' fragment” refers to a fragment formed by the assembly of the part of the heavy chain located upstream of the pepsin cleavage site (the CH1 domain and the hinge region are included, but not the other CH domains) and the whole light chain of the antibody of interest comprising two heavy chains and two light chains.. A “F(ab')2 fragment” refers to a fragment formed by the pairing of 2 Fab' fragments by disulfide bridges at the cysteines of the hinge region. A “nanobody” or “single-domain antibody” or “sdAb” refers to the variable heavy chain domain of a single-chain antibody. In particular, a nanobody can be a VHH or a VNAR. “VHH” refers to the variable domain of the heavy chain of a single-chain camelid antibody (particularly llama and alpaca). “VNAR” refers to the variable domain of the heavy chain of a single-chain antibody of cartilaginous fish (in particular shark). A VHH or VNAR generally has a molar mass of around 12 to 15 kDa. By “antibody derivative” it is herein referred to an antibody or fragment thereof that comprises, one, two, three, four, five or more amino acid substitutions, additions, deletions or modifications relative to a "parental" (or wild-type) antibody or fragment. Antibody derivatives notably include antigen-binding antibody derivatives, which retain the ability of the parental antibody to specifically bind to its antigen. The term “antibody derivatives” encompasses antibodies artificially modified, that is to say modified by genetic engineering, to alter the properties of the antibody. The term “antibody derivatives” encompasses chimeric antibodies, in particular humanized antibodies, multispecific antibodies, as well as small derivatives modified to improve their three- dimensional structures, such as scFv, diabodies, tribodies, tetrabodies, minibodies. By “scFv fragment” or “scFv” or “single-chain variable fragment” or “single-chain Fv”, it is referred to a fragment formed by the fusion of the VH domain to the VL domain of an antibody via a peptide called a “linker” consisting of a reduced number of amino acids (generally 15 to 20), either in the VH-linker-VL format or in the VL-linker-VH format. Amino acids in the linker are most often chosen from glycine, serine, threonine, asparagine, alanine and proline, with glycine and serine most often used in the majority. A common scFv format is VH-linker-VL, where the linker sequence is GGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 6). A scFv generally has a molar mass of around 25 kDa. A “diabody” refers to a dimer composed of two scFv fragments. The two scFv fragments may be identical (in which case the diabody has a single antigenic specificity) or different (in which case the diabody may be bispecific if the two scFvs recognize different antigens). A diabody generally has a molar mass of around 50 kDa (2 times that of a scFv). A “tribody’” or “triabody’” refers to a trimer composed of three scFv fragments. The three scFv fragments may be identical (in which case the tribody has a single antigenic specificity) or different (in which case the tribody may be bi- or tri-specific, depending on the antigenic specificity of the three scFvs). A tribody generally has a molar mass of around 75 kDa (3 times that of a scFv). A “tetrabody” or “tetraantibody” refers to a quadrimer composed of four scFv fragments. The four scFv fragments may be identical (in which case the tetrabody has a single antigenic specificity) or different (in which case the tetrabody may be bi-, tri- or quadri-specific, depending on the antigenic specificity of the four scFvs). A tetrabody generally has a molar mass of around 100 kDa (4 times that of a scFv). A “minibody” or “miniantibody” refers to a derivative formed by the fusion of a scFv to a domain that tends to dimerize, in particular a CH3 domain. A minibody generally has a molar mass of around 75 kDa. By “chimeric antibody” it is meant an antibody that contains a natural variable region (light chain and heavy chain) derived from an antibody of a given species in combination with the light and heavy chain constant regions of an antibody of a species heterologous to said given species. Advantageously, if the monoclonal antibody composition for use as a medicinal product according to the invention comprises a chimeric monoclonal antibody, the latter comprises human constant regions. From a non– human antibody, a chimeric antibody can be prepared by using the genetic recombination techniques well–known to a person skilled in the art. For example, the chimeric antibody can be prepared by cloning the heavy and light chains of a recombinant DNA comprising a promoter and a sequence encoding the variable region of the non–human antibody, and a sequence encoding the constant region of a human antibody. For methods for preparing chimeric antibodies, reference may be made, for example, to the document by Verhoeyen et al.–1988 (Verhoeyen et al. BioEssays, 8:74, 1988; Verhoeyen et al. Science, 239:1534– 1536, 1988). By “humanized antibody” it is meant an antibody that contains CDRs derived from an antibody of non–human origin, the other portions of the antibody molecule being derived from one (or from several) human antibodies. Moreover, certain residues of the framework regions (FR) may be modified to retain binding affinity (Jones et al.–1986; Verhoeyen et al. 1988; Riechmann et al.–1988). The humanized antibodies according to the invention can be prepared by techniques known to a person skilled in the art such as CDR grafting, resurfacing, superhumanization, human string content, FR libraries, guided selection, FR shuffling and humaneering technologies, as summarized in the review by Almagro et al.–2008 (Almagro et al. Frontiers in Bioscience 13, 1619–1633, January 1, 2008). By “multispecific antibody” it is meant an antibody engineered to target several distinct antigens or epitopes simultaneously. Typical multispecific antibodies are bispecific antibodies that specifically bind to two distinct antigens or epitopes. As used herein, the term "specifically binds" or is “specific for” a particular polypeptide or an epitope on a particular polypeptide target means binding that is measurably different from a non-specific interaction. Specific binding can be measured, for example, by determining binding of a molecule compared to binding of a control molecule, which generally is a molecule of similar structure that does not have binding activity. For example, specific binding can be determined by competition with a control molecule that is similar to the target, for example, an excess of non-labelled target. In this case, specific binding is indicated if the binding of the labelled target to a probe is competitively inhibited by excess unlabelled target. The term “specific binding” or “specifically binds to” or is “specific for” a particular polypeptide or an epitope on a particular polypeptide target as used herein can be exhibited, for example, by a molecule having a KD for the target of at least about 10-4M, alternatively at least about 10-5M, alternatively at least about 10-6M, alternatively at least about 10-7M, alternatively at least about 10-8M, alternatively at least about 10-9M, alternatively at least about 10-10M, alternatively at least about 10-11M, alternatively at least about 10-12M, or greater. As used herein, an “extracellular domain” refers to a portion of a membrane protein that extends outside the cell into the extracellular space. As used herein, a “transmembrane domain” or “TMD” refers to a structural region of a protein that is located inside the phospholipid bilayer of a cellular membrane. TMDs are typically composed of hydrophobic amino acid residues, which allows them to integrate into the hydrophobic interior of the lipid bilayer. They can consist of one or more alpha-helices or a transmembrane beta barrel structure. Their length can vary, but they are generally 15-30 amino acids long to match the thickness of the membrane. Several publicly available prediction tools can be used to predict the probability that a given protein contains a TMD and its localization, such as TMHMM (for Transmembrane Hidden Markov Model; Krogh et al., 2001, J. Mol. Biol. 305: 567-80), DeepTMHMM (Jeppe Hallgren, Konstantinos D. Tsirigos, Mads D. Pedersen, José Juan Almagro Armenteros, Paolo Marcatili, Henrik Nielsen, Anders Krogh and Ole Winther (2022). DeepTMHMM predicts alpha and beta transmembrane proteins using deep neural networks. https: / / doi.org / 10.1101 / 2022.04.08.487609) and DAS (Dense Alignment Surface, M. Cserzo, E. Wallin, I. Simon, G. von Heijne and A. Elofsson: Prediction of transmembrane alpha-helices in procariotic membrane proteins: the Dense Alignment Surface method; Prot. Eng. vol. 10, no. 6, 673-676, 1997). For example, DAS-TM filter algorithm provides a high precision hydrophobicity profile for the query from which the location of the potential transmembrane segments can be obtained. As used herein, an “intracellular domain” refers to a portion of a membrane protein that is located inside the cell. As used herein, a “signaling intracellular domain” refers to an intracellular domain within a protein that plays a crucial role in cellular signal transduction processes. A signaling intracellular domain notably refers to an intracellular portion of a membrane receptor that is responsible for transmitting signals and activating downstream cellular pathways when the membrane receptor is stimulated by binding of its ligand. A signaling intracellular domain often contains specific amino acid motifs that interact with other intracellular proteins to transmit signals. Examples of such motifs include an ITAM motif, an ITIM motif, an ITSM (Immunoreceptor Tyrosine-based Switch Motif) motif, a YMNM motif, a PYAP motif. In the context of the invention, the term “ITAM motif” (for ‘Immunoreceptor Tyrosine-based Activation Motif’) refers to a motif characterised by the repetition of the sequence of four amino acids YXXJ (wherein X is any amino acid and J is I or L), two iterations of the sequence being separated by 6 to 8 amino acid residues. The proteins CD3γ, CD3δ, CD3ε, CD3ζ, FcγRI, FcεRI, FcγRIII, CD22, CD79a, CD79b CD66d, DAP12 are for example known to contain at least one ITAM motif. An “ITIM motif” (for “Immunoreceptor Tyrosine-based Inhibitory Motif”) refers to a conserved sequence of amino acids found in the cytoplasmic domains of many inhibitory receptors in immune cells. ITIM motifs share a consensus amino acid sequence X1X2YX4X5X6, wherein X1 is selected from S, I, V and L, each of X2, X4 and X5 is any amino acid, and X6 is selected from I, V and L. ITIM motifs are found intracellularly in the cytoplasmic domains of inhibitory receptors, recruit SH2 domain-containing phosphatases (e.g., SHP-1, SHP-2, SHIP), inhibit cellular activation, often counteract ITAM (Immunoreceptor Tyrosine-based Activation Motif) signaling. ITIM motifs are found in various immune cells including T cells, B cells, NK cells, dendritic cells, macrophages, and mast cells. Examples of ITIM-containing receptors include FcγRIIB, PD-1, BTLA, CD72, NKG2A, CD31, SIGLEC family proteins, ILTs / LIRs. An “ITSM motif” (for “Immunoreceptor Tyrosine-based Switch Motif”) refers to a specific amino acid sequence found in certain immune cell receptors. The ITSM motif typically consists of the amino acid sequence TX2YX4X5X6, wherein each of X2, X4 and X5 is any amino acid and X6 is selected from V and I. ITSMs are found in the cytoplasmic tails of certain inhibitory receptors and play a crucial role in signal transduction and regulation of immune cell activation. When phosphorylated, ITSMs can recruit SH2 domain- containing proteins, particularly phosphatases like SHP-1 and SHP-2. These phosphatases can then modulate downstream signaling pathways. While similar to Immunoreceptor Tyrosine-based Inhibitory Motifs (ITIMs), ITSMs can have more complex signaling outcomes. ITSMs can potentially mediate both inhibitory and activating signals, depending on the cellular context and binding partners. ITSMs are found in signaling lymphocyte activation molecule (SLAM) family proteins. Examples of proteins comprising an ITSM motif include PD-1, and BTLA (B and T Lymphocyte Attenuator), SIRPA (Signal Regulatory Protein Alpha), CD22, FcγR2B, CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4), TIM3 (T-cell immunoglobulin and mucin domain-containing protein 3), LAG3 (Lymphocyte Activation Gene 3) and TIGIT (T cell immunoreceptor with Ig and ITIM domains). A “YMNM motif” refers to the specific amino acid sequence YMNM (SEQ ID NO: 7) found in certain proteins that plays an important role in intracellular signaling. This motif is critical for the recruitment of SH2-domain containing proteins. The most well-known protein containing the YMNM motif is CD28. A “PYAP motif” refers to the specific amino acid sequence PYAP (SEQ ID NO: 8) found in certain proteins that plays an important role in intracellular signaling. The PYAP motif binds to several important signaling proteins. The most well-known protein containing the YMNM motif is CD28. As used herein, a “signaling intracellular stimulatory domain” refers to a signaling intracellular domain comprising an ITAM, such as a signaling intracellular domain comprising an ITAM from the following proteins: CD3γ, CD3δ, CD3ε, CD3ζ, FcγRI, FcεRI, FcγRIII, CD22, CD79a, CD79b CD66d, and DAP12. As used herein, a “signaling intracellular co-stimulatory domain” refers to a signaling intracellular domain from a co-stimulatory protein. As used herein, a “co-stimulatory protein” refers to a protein that provides a secondary signal that is necessary for full T cell activation, in addition to the primary signal received through the T cell receptor (TCR). Without this co-stimulatory signal, T cells may become anergic or unresponsive even if they recognize an antigen. Co- stimulatory proteins may be divided in two main families: the CD28 family and the TNF receptor family. The CD28 family comprises at least CD28 and ICOS. The TNF receptor family comprises at least CD40L. The term “vector” as used herein refers to a nucleic acid molecule that contains the elements necessary to allow delivery, propagation and / or expression of a specific nucleic acid molecule (the “insert”) within a host cell or subject. The term “vector” has to be understood broadly as including non-natural or natural vectors such as mRNA, plasmids, viruses, episomes, cosmids, bacteriophage, and artificial chromosomes. This term encompasses cloning vectors (vectors for maintenance), expression vectors (vectors directing the expression of an insert to which they are operably linked in various host cells or subjects), extrachromosomal vectors (e.g., multicopy plasmids), integrative vectors (e.g. designed to integrate into the genome of the host cell or subject, so that they replicate whenever the host genome replicates), and shuttle vectors (e.g., functioning in both prokaryotic and eukaryotic hosts). Vectors may be of naturally occurring genetic sources, artificial, or some combination of natural and artificial genetic elements. Each vector typically contains various components; the nature of these components may vary depending on the function of the vector (e.g., cloning, expression, extrachromosomal, integration, shuttle, etc.) and the particular host cell or subject. Typically, such vectors are commercially available or available from depositary institutions such as the American Type Culture Collection (ATCC, Rockville, Md.) or have been the subject of numerous publications describing their sequence, organization and methods of producing, allowing the artisan to apply them. Components that may be present in the vector notably include: an origin of replication (at which replication is initiated), a selection marker gene and / or a reporter gene, a multicloning site (containing several distinct restriction sites), and one or more regulatory sequence(s) (e.g., a promoter, enhancer, a ribosome binding site (RBS), a signal sequence, a transcription termination sequence, etc.). The selection marker gene and / or the reporter gene are used for selection of host cells or subject carrying the vector. The multicloning site is typically used for the insertion of the insert. In the case of an expression vector, the insert is inserted so that it is operably linked to regulatory sequences present in the vector. Furthermore, the “vector” herein can be a nucleic acid molecule in any form, e.g., naked, complexed with proteins, comprised within a viral particle, etc. The present divulgation also encompasses vectors complexed to lipids or polymers to form particulate structures such as liposomes, lipoplexes or nanoparticles. The skilled person may select the appropriate vector based on general common knowledge, notably the skilled person will consider the size of the insert and the particular host cell or subject. For example, when the host cell or subject is mammalian, the skilled person may use a non-integrative vector (i.e., which does not integrate into the genome of the host cell or subject) or an integrative vector (i.e., which is stably or temporary incorporated into the genome of the host cell or subject). In the context of the invention, the term “expression vector” has to be understood broadly as including mRNA, plasmid and viral vectors. Expression vectors which are appropriate in the context of the present invention, include plasmid and viral vectors for expression in higher eukaryotic cells or subjects. Typically, such vectors are commercially available (e.g. in Invitrogen, Stratagene, Amersham Biosciences, Promega, etc.) or available from depositary institutions such as the American Type Culture Collection (ATCC, Rockville, Md.) or have been the subject of numerous publications describing their sequence, organization and methods of producing, allowing the artisan to apply them. The present invention also encompasses vectors (e.g. plasmid DNA and mRNA) complexed to lipids or polymers to form particulate structures such as liposomes, lipoplexes or nanoparticles. Preferably, the expression vector is a viral vector. As used herein a “bicistronic vector” is a type of expression vector that is designed to express two encoding polynucleotides from a single promoter in a host cell (an immune cell in the context of the invention). Typically, a bicistronic vector may comprise two encoding polynucleotides separated an IRES (Internal Ribosome Entry Site) element, or a viral 2A sequence (e.g., T2A, P2A, F2A, E2A). The term "viral vector" as used herein refers to a nucleic acid vector that includes at least one element of a virus genome and may be packaged into a viral particle. The terms “virus”, “virions”, “viral particles” and “viral vector particle” are used interchangeably to refer to viral particles that are formed when the nucleic acid vector is transduced into an appropriate cell or cell line according to suitable conditions allowing the generation of viral particles. In the context of the present invention, the term “viral vector” has to be understood broadly as including nucleic acid vector (e.g. DNA viral vector) as well as viral particles generated thereof. The term “infectious” refers to the ability of a viral vector to infect and enter into a host cell or subject. Examples of suitable viral vectors include vectors generated from a variety of different viruses (e.g. poxviruses, adenoviruses, herpes viruses, paramyxoviruses, rhabdoviruses, lentiviruses, retroviruses, parvoviruses, alphaviruses, etc). Typically, such vectors are commercially available or available from depositary institutions such as the American Type Culture Collection (ATCC, Rockville, Md.) or have been the subject of numerous publications describing their sequence, organization and methods of producing, allowing the artisan to apply them. As used herein, “operably linked” means that the elements being linked are arranged so that they function in concert for their intended purposes. For example, a promoter operably linked to a nucleic acid molecule initiates and mediates transcription of this nucleic acid molecule. Operably linked sequences include both expression control sequences that are contiguous with a nucleic acid molecule and expression control sequences that act in trans or at a distance to control a nucleic acid molecule. As used herein, the terms “replication-defective virus” denotes a virus incapable of replicating in infected cells. Generally, the genome of replication-defective viruses used in the context of the present invention hence lacks at least the sequences needed for the replication of the said virus in infected cells. These regions may be either removed (wholly or partially), or rendered non-functional, or replaced by other sequences, in particular by the recombinant polynucleotide encoding a polypeptide of interest. Preferably, a replication- defective virus nevertheless retains the sequences of its genome which are needed for encapsulation of the viral particle. As used herein, the term “regulatory elements” or “regulatory sequence” refers to any nucleic acid element(s) that allows, contributes or modulates such functions as replication, transcription, splicing, translation, stability and / or transport of a nucleic acid molecule in a given host cell or subject. Regulatory elements as used herein notably encompass appropriate transcription initiation signals, including promoter and enhancer elements, and transcription termination signals; efficient RNA processing signals such as splicing signals, ribosomal binding site (RBS) and polyadenylation signals; elements that stabilize cytoplasmic mRNA; elements that enhance translation efficiency (i.e., Kozak consensus element). It will be appreciated by those skilled in the art that the choice of the regulatory sequences can depend on such factors as the vector itself and the cells to be transfected, and will be easily selected by those skilled in the art based on common general knowledge and publications on this topic. In particular, in prokaryotes, such regulatory elements generally include promoter, ribosomal binding site, and transcription termination sequence; in eukaryotes, generally, such regulatory elements include promoters and transcription termination sequence. As used herein, the term “biological sample” or “sample” refers to a sample that has been obtained from a biological source, such as a patient or subject. A “biological sample” as used herein refers notably to a subset of a whole organism’s tissues, cells or component parts (e.g. a tumor biopsy, blood vessel, including artery, vein and capillary; body fluids, including but not limited to blood, serum, mucus, lymphatic fluid, synovial fluid, cerebrospinal fluid, saliva, amniotic fluid, amniotic cord blood, urine, vaginal fluid and semen). “Biological sample” further refers to a homogenate, lysate or extract prepared from a whole organism or a subset of its tissues, cells or component parts, or a fraction or portion thereof. Lastly, “biological sample” refers to a medium, such as a nutrient broth or gel in which an organism has been propagated, which contains cellular components, such as proteins or nucleic acid molecules. As used herein, the term “pharmaceutical composition” refers to a composition described herein, or pharmaceutically acceptable salts thereof, with other agents such as excipients. The pharmaceutical compositions as provided herewith typically include a pharmaceutically acceptable excipient. As used herein, “treatment” or “treating” refers to an improvement of the patient’s disease, disorder, or condition, which may be observed at the clinical, histological, and / or biochemical level. The terms “treating” or “treatment” notably include improving a clinical, histological, and / or biochemical symptom or parameter associated with the patient’s disease, disorder, or condition or inhibiting, reducing, or delaying progression or exacerbation of the patient’s disease, disorder, or condition (including secondary damage caused by the disease, disorder, or condition) to either a statistically significant degree or to a degree detectable to one skilled in the art. In some embodiments, treatment is assessed on a population basis such that a therapy is considered to “treat” a particular disease, disorder or condition if a statistically significant improvement of the patient’s disease, disorder, or condition is observed in a population suffering from the disease, disorder, or condition. In the context of the invention, the terms "prevent", "prevention" and "preventing" refer to the reduction in the risk for a subject of acquiring or developing a given disease, disorder, or condition. The terms "prevent", "prevention" and "preventing" also comprise delaying the onset and / or reducing the frequency and / or intensity of clinical, histological and / or biochemical symptoms or parameters associated with this given disease, disorder, or condition. In some embodiments, prevention is assessed on a population basis such that a therapy is considered to “prevent” a particular disease, disorder or condition if a statistically significant decrease in the risk of acquiring or developing the disease, disorder, or condition, and / or a statistically significant delay of the onset and / or a statistically significant decrease of the frequency and / or intensity of clinical, histological and / or biochemical symptoms or parameters associated with the disease, disorder or condition, is observed in a population susceptible to the disease, disorder, or condition. In the context of the invention, the terms “therapeutically effective amount” refer to an amount effective of a therapeutic agent, at dosages and for periods of time necessary, to elicit the desired biological response in a subject. In other words, the therapeutic effective amount is the amount of the therapeutic agent which is sufficient to reduce and / or ameliorate the severity and / or duration of a given disease, disorder or condition and / or a symptom related thereto. The therapeutical effective amount will be adjusted to the individual requirements in each particular case. It can vary within wide limits depending upon numerous factors such as the nature and the severity of the disease, disorder or condition to be treated, the age and general health condition of the patient, other medicaments with which the patient is being treated, the route and form of administration and the preferences and experience of the medical practitioner involved. In the context of the invention, a “subject” may be any of mammalian animals including human, dog, cat, cattle, goat, pig, swine, sheep and monkey, preferably a human. A human subject can be known as a patient. In the context of the invention, the term “chemotherapy” refers to any therapy involving small molecules that is to say chemical compounds, for the treatment of cancer, and encompasses therapy using the chemotherapeutic agents as defined herein. In the context of the invention, the term “immunotherapy” refers to any therapy involving molecules that inhibit or stimulate the body's own immune system, for the treatment of cancer, and encompasses therapy using immunotherapy agents as defined herein. In the context of the invention, the terms “hormone therapy” refers to any therapy involving hormones or hormone-blocking drugs, for the treatment of cancer, and encompasses therapy using hormone therapy agents as defined herein. In the context of the invention, the term “radiotherapy” refers to treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. The terms “cell proliferative disorder” and “proliferative disorder” herein refer to disorders that are associated with some degree of abnormal cell proliferation. In some embodiments, the cell proliferative disorder is a tumour or cancer. “Tumour,” as used herein, refers to all neoplastic cell growth and proliferation, whether malignant or benign, and all pre-cancerous and cancerous cells and tissues. The terms “cancer,” “cancerous”, “cell proliferative disorder”, “proliferative disorder” and “tumour” are not mutually exclusive as referred to herein. The terms “cancer” and “cancerous” refer to or describe the physiological condition in mammals that is typically characterised by unregulated cell growth. A “cancer” as used herein is any malignant neoplasm resulting from the undesired growth, the invasion, and under certain conditions metastasis of impaired cells in an organism. The cells giving rise to cancer are genetically impaired and have usually lost their ability to control cell division, cell migration behaviour, differentiation status and / or cell death machinery. Most cancers are “solid cancers”, i.e. mass of solid cancer cells that grows in organ systems and can appear anywhere in the body. But other cancers are “liquid cancers” (also referred to as “haematological cancers”), i.e. cancers that develop in the blood, bone marrow, or lymph nodes, and include leukemia, lymphoma, and myeloma. In the context of the invention, the terms “solid cancer resistant to radiation therapy” or “solid tumor resistant to radiation therapy” refer to solid tumors which are known as or can be identified as being resistant to radiation therapy, that is to say as tumors which are known as or can be identified as having a therapeutic response below average to radiation therapy. In the context of the invention, a therapeutic response is considered as below average when it is significantly lower than the mean therapeutic effect obtained in cancers or tumors of reference, when treated with the same treatment. The person skilled in the art may thus identify on this basis whether a specific solid cancer or tumor is resistant to radiation therapy. Some cancers are known in the art as being resistant to radiation therapy. In the context of the invention, cancers or tumors known as being resistant to radiation therapy are cancers or tumors which have demonstrated resistance to radiation therapy based on clinical criteria. More specifically solid tumors or solid cancers are generally considered in the art as “resistant to radiation therapy” if recurrences, also called local relapses, are observed within six months following the first course of radiation therapy (Hutchinson, MK.N.D. et al.). In other terms, solid tumors which have been treated with a first course of radiation therapy and have relapsed within six months following the end of said first course are generally considered in the art as meeting the criteria for “solid tumor resistant to radiation therapy”. Some cancers are known in the art as being sensitive to radiation therapy, such as for instance seminomas, medulloblastoma, neuroblastoma, Wilm’s tumor, early cervical carcinoma, vaginal carcinoma, for which radiation therapy results in a positive response in most patients. A second category are cancers or tumors known as being resistant to radiation therapy, based on biological criteria. More specifically solid tumors or solid cancers are also generally considered in the art as “resistant to radiation therapy” if they can be associated with biological markers of intrinsic or acquired resistance mechanisms involving the DNA damage response, tumor aneuploidy, the anti-apoptotic proteins such as BCL-2 and BCL-XL, the alteration of glucose metabolism pathway, hypoxia or the overexpression of negative immune modulators such as the ecto-5'-nucleotidase CD73, PD-L1 or CD47. A solid tumor or solid cancer can be considered as associated with biological markers of intrinsic or acquired resistance mechanisms involving a protective DNA damage response for instance when the Mre11-Rad50-Nbs1 complex (encoded respectively by the genes Gene ID: 4361, 10111, 821254) or the protein TRIP13 (encoded by the gene: Gene ID: 9319), or the protein Ku80 (encoded by the gene: Gene ID: 7520), is overexpressed in the tumor or in the biological tissues surrounding it, compared with healthy tissues of similar embryonic origin. Such cancer or tumor may be designated as overexpressing the Mre11-Rad50-Nbs1 complex, TRIP13, or Ku80. A solid tumor or solid cancer can be considered as associated with biological markers of tumor aneuploidy for instance when several cells in the tumors contain an abnormal number of chromosomes, as measured by the karyotype. Such cancer or tumor may be designated as aneuploid. A solid tumor or solid cancer can be considered as associated with resistance mechanisms that imply BCL-2 and / or BCL-XL when BCL-2 (encoded by the gene: Gene ID: 596), and / or BCL-XL (encoded by the gene: Gene ID: 598), is overexpressed in the tumor or in the biological tissues surrounding it. Such cancer or tumor may be designated as overexpressing BCL-2 and / or BCL-XL. A solid tumor or solid cancer can be considered as associated with biological markers of the alteration of glucose metabolism pathway, such as AKT-mediated enhanced aerobic glycolysis, when the protein AKT (encoded by the gene: Gene ID: 5207), is overexpressed in the tumor or in the biological tissues surrounding it. Such cancer or tumor may be designated as overexpressing AKT. A solid tumor or solid cancer can be considered as associated with biological markers of hypoxia, such as the HIF subunit genes, when the protein HIF-1α and / or HIF-2α (encoded respectively by the genes: Gene ID: 3091 and 2034), is overexpressed in the tumor or in the biological tissues surrounding it. Such cancer or tumor may be designated as overexpressing HIF-1α and / or HIF-2α. A solid tumor or solid cancer can be considered as associated with overexpression of negative immune modulators, for instance when CD73, PD-L1 or CD47 (encoded respectively by the genes: Gene ID: 4907, 100196322 and 961), is overexpressed in the tumor or in the biological tissues surrounding it. Such cancer or tumor may be designated as overexpressing CD73, PD-L1 or CD47. Genetically modified immune cell In the context of the present invention, the inventors surprisingly found that the adoptive transfer of genetically-engineered monocytes overexpressing p21 and expressing at their surface a chimeric antigen receptor (CAR) or cell binder (CB) specifically binding to an antigen of cancer cells into mouse preclinical cancer models of led to their differentiation into phagocytosis-proficient tumor-associated macrophages (TAMs) that after tumor cell engulfment underwent proinflammatory activation and supported cancer regression. They further demonstrated that genetically-engineered monocytes combining p21 overexpression with a CAR or CB displayed significantly improved cancer cell phagocytosis (and in particular polyphagocytosis) and proinflammatory activation after tumor phagocytosis than genetically-engineered monocytes with either p21 overexpression or a CAR. Combining both approaches thus resulted in synergistic improvement of anticancer efficiency in several cancers, including cancers with bad prognosis such as triple-negative breast cancer (see Examples). The present invention therefore first relates to a genetically modified immune cell, which: (a) overexpresses p21 compared to a corresponding non-genetically modified immune cell, (b) expresses at its surface a means for binding an antigen, preferably a recombinant antigen-binding domain, and (c) is a monocyte, a macrophage, a dendritic cell or a precursor any of these cells. Preferably, the genetically modified immune cell is an immune cell comprising a recombinant polynucleotide (one or more), which preferably encodes an expression product (one or more), such as an mRNA or a recombinant polypeptide, which may be exogenous or endogenous to the cell. The genetically modified immune cell preferably comprises a recombinant polynucleotide encoding an exogenous recombinant polypeptide, more preferably an allogenic exogenous recombinant polypeptide (such as an antigen-binding domain, optionally fused to a transmembrane domain). The genetically modified immune cell may also comprise both a recombinant polynucleotide encoding an exogenous recombinant polypeptide, more preferably an allogenic exogenous recombinant polypeptide (such as an antigen-binding domain, optionally fused to a transmembrane domain), and a recombinant polynucleotide encoding an endogenous polypeptide (such as a p21 protein). The invention also relates to a genetically modified immune cell, wherein the immune cell is a monocyte, macrophage, dendritic cell or precursor thereof which expresses at its surface a recombinant antigen binding domain, wherein the genetically modified immune cell overexpresses p21 compared to a corresponding non-genetically modified immune cell. The invention also relates to: Vectors or expression vectors for producing said genetically modified immune cell, which can be administered in vivo or ex vivo, wherein said vectors comprise: i) a nucleic acid encoding a first recombinant polynucleotide, or a first vector comprising a first recombinant polynucleotide, wherein the first recombinant polynucleotide encodes a CB, e.g. a recombinant antigen-binding domain as defined herein or a fusion polypeptide comprising a recombinant antigen-binding domain and a transmembrane domain as defined herein, and a second recombinant polynucleotide, or a second vector comprising a second recombinant polynucleotide, wherein the second recombinant polynucleotide encodes a p21 protein, or ii) a recombinant polynucleotide, or a vector comprising a recombinant polynucleotide, wherein the recombinant polynucleotide encodes (1) a recombinant antigen-binding domain as defined herein or a fusion polypeptide comprising a recombinant antigen-binding domain and a transmembrane domain as defined herein, and (2) a p21 protein. Immune cell The genetically modified immune cell is a monocyte, a macrophage, a dendritic cell or a precursor of any of these cells. In a preferred embodiment, the immune cell is a monocyte, more preferably a monocyte purified from a blood sample, in particular from a sample of peripheral blood mononuclear cells (PBMC). In some embodiments, the immune cell is positive for one or more surface marker(s) selected from CD33, CD14, CD11b, CD16, and CD11c. In some embodiments, the immune cell is positive for the surface marker CD11b, CD14 or for both CD11b and CD14. In some embodiments, the immune cell is also positive for the marker CD16. The immune cell may preferably also be negative for surface markers of immune cells other than monocytes, macrophages, dendritic cells and their precursors, such as CD56 (marker of NK cells), CD3 (marker of T cells) and CD19 and CD20 (markers of B cells). The genetically modified immune cell is preferably a human genetically modified immune cell. In some embodiments, the genetically modified immune cell is isolated, or is ex vivo. P21 overexpression According to the invention, the genetically modified immune cell overexpresses p21 compared to a corresponding non-genetically modified immune cell. In some embodiments, overexpression of p21 is achieved by expressing, in the genetically modified immune cell, an exogenous polynucleotide encoding p21 polypeptide. In some embodiments, overexpression of p21 is achieved by delivering, in vivo, an immune cell, or a polynucleotide (such as an mRNA) encoding p21 polypeptide. Test for determining overexpression Overexpression of p21 by the genetically modified immune cell according to the invention compared to a corresponding non-genetically modified immune cell, can be performed by any appropriate method. For this purpose, the expression level of p21 in the genetically modified immune cell according to the invention is compared to the expression level of p21 in the corresponding non-genetically modified immune cell. The expression level of p21 in the genetically modified immune cell according to the invention may be compared to the expression level of p21 in the corresponding non- genetically modified immune cell at either the protein or the mRNA level. The expression level of p21 protein may be measured by any appropriate method, including but not limited to immunoassays, such as Enzyme-Linked Immunosorbent Assay (ELISA) and Western blot; mass spectrometry-based methods, such as selected reaction monitoring (SRM), multiple reaction monitoring (MRM) and parallel reaction monitoring (PRM); and fluorescence-based methods, such as fluorescence resonance energy transfer (FRET), flow cytometry, radioimmunoassay (RIA) and aptamer-based assays. Western blot and flow cytometry are preferred. A specific method for measuring the expression level of p21 protein by western blot is disclosed in WO2021 / 013764. When the expression level of p21 is measured and the genetically modified immune cell has been transformed by, it is preferably measured in the genetically modified cell. The expression level of p21 mRNA may be measured by any appropriate method, including but not limited to reverse transcription quantitative PCR (RT-qPCR); RNA sequencing (RNA-Seq); Northern Blotting; Nuclease Protection Assays; In Situ Hybridization. RT-qPCR and RNA-Seq are preferred, in particular RT-qPCR. RT-qPCR involves: 1. Reverse transcription of mRNA to cDNA using a retrotranscriptase (e.g. SuperScript II RT available from Invitrogen), 2. Amplification of the cDNA using specific primers, 3. Real-time monitoring of amplification using fluorescent dyes (e.g. sybrgreen) or probes (e.g. Taqman probes), 4. Quantification based on amplification curves and cycle thresholds. RNA-seq involves: 1. Preparing cDNA libraries from RNA samples, 2. High-throughput sequencing of the cDNA, and 3. Bioinformatic analysis to quantify transcript abundance. A specific RT-qPCR method for measuring the expression level of p21 mRNA in a cell is disclosed in Allouch, A. et al., 2022. In this method, total RNA is extracted from the cell using a conventional method or kit (such as the with the RNeasy kit available from Qiagen), retrotranscribed into cDNA using a retrotranscriptase (preferably SuperScript II RT available from Invitrogen), and the expression level of p21 cDNA is then measured by quantitative PCR, preferably using a Taqman® p21 assay using primers specifically binding to p21 and a a Taqman® probe specifically binding to p21, such as the Hs00355782_m1 assay available from ThermoFisher. This assay amplifies and specifically detects with the Taqman probe an amplicon of 66 nucleotides starting at nucleotide 566 of Genbank RefSeq NM_000389.4. However, any other qPCR assay specifically amplifying and detecting p21 cDNA can be used instead. When the genetically modified immune cell has been transformed by a second recombinant polynucleotide or a second vector comprising a second recombinant polynucleotide, wherein the second recombinant polynucleotide encodes a p21 protein, and the expression level of p21 is measured at the mRNA level, the measure is preferably performed at least 24 hours after transformation, more preferably by RT-qPCR. Induction of overexpression The genetically modified immune cell may overexpress p21 compared to a corresponding non-genetically modified immune cell either constitutively (preferred constitutive embodiment) or in response to specific stimuli or environmental conditions (alternative inducible embodiment). In any case, the genetic modifications made to the immune cell contribute at least in part to the immune cell overexpressing p21 compared to a corresponding non-genetically modified immune cell. Preferably, the immune cells are genetically modified so that the overall expression of p21 is preferably at least two or three times higher than in in corresponding non- genetically modified immune cell. In a preferred embodiment, genetic modifications including transfer into the immune cell of a recombinant polynucleotide or a vector comprising a recombinant polynucleotide, wherein the recombinant polynucleotide encodes, under the control of appropriate regulatory sequences, a p21 protein or another protein, which overexpression results in upregulation of p21 protein expression. Preferably, in the inducible embodiment, the genetically modified immune cell overexpresses p21 compared to a corresponding non-genetically modified immune cell in response to inducers of expression, in particular chosen in the list consisting of tetracycline, doxycycline, and anhydrotetracycline (ATC). This may be obtained by inserting genetic modifications including transfer into the cell of a recombinant polynucleotide encoding under the control of an inducible promoter a p21 protein or another protein, which overexpression results in upregulation of p21 protein expression, such as tetracycline-inducible, doxycycline-inducible, and anhydrotetracycline (ATC)- inducible promoters. In the constitutive embodiment, the genetic modifications may include transfer into the cell of a recombinant polynucleotide encoding under the control of a constitutive promoter a p21 protein or another protein, which overexpression results in upregulation of p21 protein expression. In a preferred embodiment the genetically modified immune cell of the invention comprises a recombinant polynucleotide, or vector comprising a recombinant polynucleotide, wherein the recombinant polynucleotide encodes under the control of appropriate regulatory sequences a p21 protein. The sequence encoding p21 protein may be any nucleotide sequence encoding the p21 protein of sequence SEQ ID NO: 2 (human sequence), or SEQ ID NO: 4 (murine sequence), or any functional variant or fragment thereof. The nucleotide sequence may preferably be optimized for expression in the targeted host / species (e.g. optimized for mammalian expression when use is intended in humans or other mammals, optimized for human expression when use is intended in humans…). Specific examples of a sequence encoding p21 protein are SEQ ID NO: 1 (human p21), SEQ ID NO: 3 (mouse p21) and SEQ ID NO: 5. In an even more particularly preferred embodiment, the genetically modified immune cell according to the invention has been transduced by a vector (e.g. a lentiviral vector) comprising the nucleic acid sequence SEQ ID NO: 5 encoding p21 protein or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO: 5 encoding p21 protein. In an alternative particularly preferred embodiment, the genetically modified immune cell according to the invention has been transduced by a vector (e.g. a lentiviral vector) comprising the nucleic acid sequence SEQ ID NO: 9 encoding encoding p21 protein and a chimeric antigen receptor specifically binding to HER2, or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO:9 encoding encoding p21 protein and a chimeric antigen receptor specifically binding to HER2. In another embodiment, the genetically modified immune cell according to the invention has been transduced by a vector (e.g. a lentiviral vector) comprising the nucleic acid sequence SEQ ID NO: 43 encoding encoding p21 protein and a HER2 specific cell binder, or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO:43 encoding encoding p21 protein and a HER2 specific cell binder. In an embodiment, the genetically modified immune cell according to the invention has been transduced by a vector (e.g. a lentiviral vector) comprising the nucleic acid sequence SEQ ID NO: 33 encoding encoding p21 protein and a chimeric antigen receptor specifically binding to GD2, or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO:33 encoding encoding p21 protein and a chimeric antigen receptor specifically binding to GD2. In an embodiment, the genetically modified immune cell according to the invention has been transduced by a vector (e.g. a lentiviral vector) comprising the nucleic acid sequence SEQ ID NO: 35 encoding encoding p21 protein and a cell binder specifically binding to GD2, or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO:35 encoding encoding p21 protein and a cell binder specifically binding to GD2. In an embodiment, the genetically modified immune cell according to the invention has been transduced by a vector (e.g. a lentiviral vector) comprising the nucleic acid sequence SEQ ID NO: 45 encoding encoding p21 protein and a chimeric antigen receptor specifically binding to Nectin-4, or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO:45 encoding encoding p21 protein and a chimeric antigen receptor specifically binding to Nectin-4. In an embodiment, the genetically modified immune cell according to the invention has been transduced by a vector (e.g. a lentiviral vector) comprising the nucleic acid sequence SEQ ID NO: 37 encoding encoding p21 protein and a cell binder specifically binding to Nectin-4, or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO:37 encoding encoding p21 protein and a cell binder specifically binding to Nectin-4. In an embodiment, the genetically modified immune cell according to the invention has been transduced by a vector (e.g. a lentiviral vector) comprising the nucleic acid sequence SEQ ID NO: 39 encoding encoding p21 protein and a chimeric antigen receptor specifically binding to Claudin 18.2, or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO:39 encoding encoding p21 protein and a chimeric antigen receptor specifically binding to Claudin 18.2. In an embodiment, the genetically modified immune cell according to the invention has been transduced by a vector (e.g. a lentiviral vector) comprising the nucleic acid sequence SEQ ID NO: 41 encoding encoding p21 protein and a cell binder specifically binding to Claudin 18.2, or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO:41 encoding encoding p21 protein and a cell binder specifically binding to Claudin 18.2. Means for binding an antigen According to the invention, the genetically modified cell also expresses at its surface means for binding an antigen, preferably a recombinant antigen-binding domain, as defined herein. In the context of the invention, the means for binding an antigen may be any molecule or region or domain thereof, which is capable of specific binding to an antigen of interest. Recognized antigen The person skilled in the art may chose the antigen of interest according to any intended use of the invention and will be able to adapt the invention by choosing the corresponding means for binding an antigen, preferably antigen-binding domain, accordingly. Preferred antigens are cancer / tumor antigens and antigens of pathogens (the latter preferably selected from antigens of eukaryotic or prokaryotic pathogens). In some embodiments the antigen is a solid tumor antigen. Yet, preferred antigens to which the recombinant antigen-binding domain expressed at the surface of the genetically modified immune cell according to the invention binds are selected from the group consisting of CD19 (also known as B4; CVID3), HER2 (also known as ERBB2; NEU; NGL; TKR1; CD340; HER-2; VSCN2; MLN 19; MLN-19; c- ERB2; c-ERB-2; HER-2 / neu; p185(erbB2)), GD2 (a disialoganglioside, CAS registry number 65988-71-8), OAcGD2 (O-acetyl-GD2), Claudin 18.2 (also known as CLDN18.2), Nectin-4 (also known as LNIR, PVRL4, PRR4), GPC3 (also known as SGB; DGSX; MXR7; SDYS; SGBS; OCI-5; SGBS1; GTR2-2), MSLN (also known as mesothelin ; MPF; SMRP), B7-H3 (also known as CD276; B7H3; B7-H3; B7RP-2; 4Ig-B7-H3), MUC1 (also known as mucin 1 ; EMA; MCD; PEM; PUM; KL-6; MAM6; MCKD; PEMT; CD227; H23AG; MCKD1; MUC-1; ADMCKD; ADTKD2; Ca15-3; ADMCKD1; CA 15-3; MUC-1 / X; MUC1 / ZD; MUC-1 / SEC), CEA (also known as Carcinoembryonic antigen); , EGFR (also known as epidermal growth factor receptor ; ERBB; ERRP; HER1; mENA; ERBB1; NNCIS; PIG61; NISBD2), PSMA (also known as folate hydrolase 1; FOLH1 ; PSM; FGCP; FOLH; GCP2; PSMA; mGCP; GCPII; NAALAD1), EPCAM (also known as epithelial cell adhesion molecule ; ESA; KSA; M4S1; MK-1; DIAR5; EGP-2; EGP40; KS1 / 4; MIC18; TROP1; BerEp4; EGP314; HNPCC8; LYNCH8; MOC-31; Ber-Ep4; TACSTD1), EGFRVIII (a mutated version of EGFR), IL13RA2 (also known as interleukin 13 receptor subunit alpha 2 ; CT19; IL-13R; IL13BP; CD213A2), CD133 (also known as prominin 1 ; PROM1 ; RP41; AC133; MCDR2; STGD4; CORD12; PROML1; MSTP061), CD47 (also known as IAP; OA3; MER), CD24 (also known as CD24A), MAGE-A4 (also known as MAGE family member A4 ; CT1.4; MAGE4; MAGE4A; MAGE4B; MAGE-41; MAGE-X2), TROP2 (also known as tumor associated calcium signal transducer 2 ; TACSTD2 ; EGP1; GP50; M1S1; EGP-1; GA7331; GA733-1), BCMA (also known as TNF receptor superfamily member 17 ; TNFRSF17 ; BCM; CD269; TNFRSF13A), CD22 (also known as SIGLEC2; SIGLEC-2), CD7 (also known as GP40; TP41; Tp40; LEU-9), CD30 (also known as TNF receptor superfamily member 8 ; TNFRSF8 ; Ki-1; D1S166E), CD20 (also known as membrane spanning 4-domains A1 ; MS4A1 ; B1; S7; Bp35; FMC7; CVID5; LEU-16), CD123 (also known as interleukin 3 receptor subunit alpha ; IL3RA ; IL3R; IL3RX; IL3RY; IL3RAY; hIL-3Ra; IL-3R-alpha), CD38 (also known as ADPRC1; cADPR1; ADPRC 1), CD33 (also known as p67; SIGLEC3; SIGLEC-3; CD33rSiglec), CD138 (also known as syndecan 1 ; SDC1 ; SDC; SYND1; syndecan), CCL-1 (also known as C-C motif chemokine ligand 1 ; P500; SISe; TCA3; I-309; SCYA1), SLAMF7 (also known as SLAM family member 7 ; 19A; CS1; CD319; CRACC), CD5 (also known as T1; LEU1), NKG2D ligands (MICA (MHC class I chain-related molecule A), MICB (MHC class I chain-related molecule B), ULBP-1 (or RAET1I), ULBP-2 (or RAET1H), ULBP-3 (or RAET1N), ULBP-4 (or RAET1E), ULBP-5 (or RAET1G) and ULBP-6 (or RAET1L)), NKG2D (also known as killer cell lectin like receptor K1 ; KLRK1 ; KLR; CD314; NKG2-D; D12S2489E), CD79b (also known as B29; IGB; AGM6; Igbeta), CD70 (also known as CD27L; LPFS3; CD27-L; CD27LG; TNFSF7; TNLG8A), ROR1 (also known as receptor tyrosine kinase like orphan receptor ; NTRKR1; dJ537F10.1), FLT3 (also known as fms related receptor tyrosine kinase 3 ; FLK2; STK1; CD135; FLK-2), CD97 (also known as adhesion G protein- coupled receptor E5 ; ADGRE5 TM7LN1), CD99 (also known as MIC2; HBA71; MIC2X; MIC2Y; MSK5X), CD18 (also known as integrin subunit beta 2 ; ITGB2 ; LAD; MF17; MFI7; LCAMB; LFA-1; MAC-1), CDH6, ROR2, RT4 / TPBG, CDH17, DLK1, EDB-fibronectin, B7-H7 / HHLA2, Claudin 6, MUC16, Claudin 1, and HER3. In some embodiments, the recombinant antigen-binding domain is capable of specific binding to, or binds specifically to, a tumor antigen, in particular a solid tumor antigen. Preferably, the recombinant antigen-binding domain is capable of specific binding to, or specifically binds to, an antigen selected from the group consisting of CD19, HER2, GD2, OAcGD2, Nectin-4, Claudin 18.2, GPC3, MSLN, B7-H3, MUC1, CEA, EGFR, PSMA, EPCAM, EGFRVIII, ILI3RA2, CD133, CD47, CD24, MAGE-A4, TROP2, BCMA, CD22, CD7, CD30, CD20, CD123, CD38, CD33, CD138, CCL-1, SLAMF7, CD5, NKG2D ligands (MICA, MICB, ULBP-1, ULBP-2, ULBP-3, ULBP-4, ULBP-5 and ULBP-6), NKG2D, CD79b, CD70, ROR1, FLT3, CD97, CD99 and CD18. In some embodiments, the recombinant antigen-binding domain is capable of specific binding to, or binds specifically to, an antigen selected from the group consisting of HER2, GD2, Nectin-4, and Claudin 18.2. Recombinant antigen-binding domain Preferably, the genetically modified cell also expresses at its surface a recombinant antigen-binding domain. The recombinant antigen-binding domain of the genetically modified immune cell according to the invention is intended to target it to cells expressing the recognized antigen at their surface. In the context of the invention, the person skilled in the art may use any domain capable of binding to an antigen of interest. These include, without be limited to, ligand- binding domain, such as ligand binding domains found in receptors, EF Hand binding domains, and immunoglobulin-like antigen binding domains such as those found in antibodies. Immunoglobulin-like antigen binding domains are of particular interest as the person skilled in the art can easily generate antibodies against an antigen of interest using usual techniques and obtain antigen-binding domains with high affinity and specificity. Antibodies, antibody derivatives and antibody fragments are well known in the art and are thus of particular interest in the context of the invention, for their well-known structures and properties. In a preferred embodiment, the recombinant antigen-binding domain thus comprises an antigen-binding domain of an antibody. The antigen-binding domain of an antibody is preferably selected from antibodies, antibody fragments and derivatives thereof, and notably from Fv fragments, Fab fragments, Fab’ fragments, F(ab’)2fragments, nanobody fragments, scFv, diabodies, tribodies, tetrabodies, and minibodies. More preferably, the antigen-binding domain of an antibody is selected from nanobodies, such as VHH and VNAR, and scFv. Such fragments and derivatives may be obtained from antibodies by methods well known in the art. Antibodies specifically binding to many antigens are available in the art, either because a cell clone producing the antibody (e.g. a hybridoma) is available in public collections (e.g. ATCC, ECCAC, DSM…) or because the amino acid sequences of their VH and VL domains, their VHH or their VNAR are known, and a skilled person will be able to identify suitable antibodies against most antigens. With respect to the preferred cancer antigens described herein, antibodies specifically recognizing them are available to the skilled person, including but not limited to: • CD19: Blinatumomab, Tafasitamab, Loncastuximab tesirine • HER2: Trastuzumab, Pertuzumab • GD2: Dinutuximab, Dinutuximab-beta, Naxitamab (also known as Hu3F8), an antibody comprising a VH domain of sequence SEQ ID NO: 10 and a VL domain of sequence SEQ ID NO: 11; • OAcGD2: an antibody comprising a VH domain of sequence SEQ ID NO: 12 (corresponding to SEQ ID NO: 76 as disclosed in WO2018 / 010846) and a VL domain of sequence SEQ ID NO: 13 (corresponding to SEQ ID NO: 112 as disclosed in WO2018 / 010846) (preferably an antibody comprising a VH domain with an amino acid sequence selected from SEQ ID NOs: 14 to 23, corresponding respectively to SEQ ID NOs: 3-5, 131-133 and 136-139 as disclosed in WO2018 / 010846 and a VL domain with an amino acid sequence selected from SEQ ID NOs: 24 to 30, corresponding respectively to SEQ ID NOs: 8-11, 134- 135 and 140 as disclosed in WO2018 / 010846); • Claudin 18.2: Zolbetuximab, Claudiximab (IMAB362 scFv), • Nectin-4: Enfortumab; • GPC3: codrituzumab, • MSLN: amatuximab, anetumab, inezetamab, misitatug, • B7-H3: ifinatamab, enoblituzumab, • MUC1: cantuzumab, clivatuzumab, gatipotuzumab, sontuzumab • CEA: arcitumomab, cergutuzumab, cibisatamab, labetuzumab,tusamitamab, • EGFR: Cetuximab, Panitumumab, Nimotuzumab, Necitumumab, • PSMA: pelgifatamab, rosopatamab, • EPCAM: catumaxomab, edrecolomab, adecatumumab, solitomab, • EGFRVIII: Cetuximab, • CD47: lemzoparlimab, ligufalimab, magrolimab, zeripatamig, urabrelimab, • TROP2: sacituzumab govitecan, datopotamab deruxtecan, Sacituzumab tirumotecan, • BCMA: teclistamab-cqyv, elranatamab-bcmm, linvoseltamab, vonsetamig, ingitamig, alnuctamab, pacanolotamab, ispectamab ebotansine, pavurutamab, • CD22: inotuzumab ozogamicin, moxetumomab pasudotox-tdfk, suciraslimab, pinatuzumab vedotin, epratuzumab tetraxetan, • CD7: cusatuzumab, vorestuzumab, Grisnilimab, • CD30: brentuximab vedotin, acimtamig, iratumumab, • CD20: Rituximab, Ofatumumab, Veltuzumab, Ocrelizumab, Obinutuzumab, Ublituximab, Ibritumomab, Tositumomab, Ripertamab, Ocaratuzumab, Mosunetuzumab, • CD123: Bexatamig, Flotetuzumab, Mipletamig, Pivekimab, Talacotuzumab, Vibecotamab, • CD38: Daratumumab, Erzotabart, Felzartamab, Isatuximab, Lumrotatug, Mezagitamab, Modakafusp, • CD33: gemtuzumab ozogamicin, avitotamig, eluvixtamab, emerfetamab, lintuzumab, vadastuximab talirine, • CD138: indatuximab, • SLAMF7: elotuzumab, azintuxizumab, • NKG2D: Tesnatilimab, Azerutamig, • CD79b: polatuzumab, • CD70: cusatuzumab, vorsetuzumab, • ROR1: zilovertamab • FLT3: Emirodatamab, • CD18: rovezulimab, • CDH6: CUSP06, Raludotatug deruxtecan (DS-6000a), QLS5133, • ROR2: Ozuriftamab vedotin (BA3021), • 5T4 / TPBG: ACR246, ASN004, SYD1875, PF-06263507, Naptumomab estafenatox, ABD320, • CDH17: 7MW4911, AMT-676, YL217, HS-20110, ARR-217, CM518D1, SOT109, LM- 350, HDM2017, • DLK1: ADCT-701, • EDB-Fibronectine: PYX-201 (micvotabart pelidotin), • B7-H7 / HHLA2: NPX267, NPX125, • IL13RA2: 52B8, • CD133: CMab-43, and • CD24: ATG-031, PHST001, ATG1144, Suvonstobart, • Claudin 6: Ixotatug (P1), DS-9606 (P1), CTIM-76 (P1), ASP1650 (IMAB027), • MUC16: Abagovomab (Discontinued), Sofituzumab (Discontinued), DMUC4064A (P1), • Claudin 1: Eclutatug (P1 / 2), lixudebart (P2), and • HER3: Patritumab (P3). Fusion polypeptide further comprising a transmembrane domain The recombinant antigen-binding domain is expressed at the surface of the genetically modified cell according to the invention. This may be obtained by covalent or non-covalent attachment to the cell membrane. For non-covalent attachment, the recombinant antigen-binding domain may further comprise a ligand domain able to bind to a molecule present at the surface of the immune cell. The ligand domain may be a polypeptide or another type of molecule able to bind to a molecule present at the surface of the immune cell. When the ligand domain is a polypeptide, it may be fused to the antigen-binding domain. For covalent attachment, the recombinant antigen-binding domain may further comprise a ligand domain able to insert itself into the cell membrane. The ligand domain may be a polypeptide or another type of molecule able to insert itself into the cell membrane (such as some lipids). When the ligand domain is a polypeptide, it is preferably a transmembrane domain. More preferably, the recombinant antigen-binding domain is then part of a fusion polypeptide further comprising a transmembrane domain. Even more preferably the fusion polypeptide comprises the recombinant antigen-binding domain fused to the transmembrane domain, optionally by a linker (preferably a peptide linker). Thus, in some embodiments the recombinant antigen-binding domain is in the form of a fusion polypeptide comprising the recombinant antigen-binding domain (preferably an antigen-binding domain of an antibody) and a transmembrane domain. Preferably, the transmembrane domain comprises a transmembrane region from a molecule selected from the group consisting of the alpha, beta or zeta chain of the T-cell receptor, CD28, CD3ε, CD45, CD4, CD5, CD8, CD9, CD 16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, CD154, Toll-like receptor 1 (TLR1), TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, and TLR9. Preferably, the transmembrane domain is the transmembrane domain of CD8. In some embodiments, the recombinant antigen binding domain (preferably an antigen-binding domain of an antibody) is connected to the transmembrane domain by a hinge domain. Preferably, the hinge domain is a hinge domain of a molecule selected from the group consisting of the alpha, beta or zeta chain of the T-cell receptor, CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137 and CD154. Preferably, the hinge domain is the hinge domain of CD8. In some embodiments, the hinge domain derives from the same protein as the transmembrane domain. Preferably the hinge domain is CD8 hinge domain (in particular CD8α) and the transmembrane domain is CD8 transmembrane domain (in particular CD8α). In a particularly preferred embodiment, the genetically modified immune cell according to the invention thus expresses at its surface a fusion polypeptide comprising the recombinant antigen-binding domain (preferably an antigen-binding domain of an antibody) fused to a transmembrane domain, or fused to a hinge domain and transmembrane domain, optionally through a linker (preferably a peptide linker). The fusion polypeptide may or may not further comprise an intracellular domain. When an intracellular domain is present, it may be devoid of a signaling intracellular domain or may comprise a signaling intracellular domain. In some embodiments, the fusion polypeptide does not comprise an intracellular domain. In some embodiments, the fusion polypeptide further comprises a signaling intracellular domain. In some embodiments, the fusion polypeptide further comprises an intracellular domain and is devoid of a signaling intracellular domain. Exemplary recombinant antigen-binding domains thus include a fusion polypeptide comprising, or consisting of: i) recombinant antigen binding domain-linker-transmembrane domain; ii) recombinant antigen binding domain-linker-hinge-linker- transmembrane domain; iii) recombinant antigen binding domain-linker-transmembrane domain- linker-intracellular domain; iv) recombinant antigen binding domain-linker-hinge-linker- transmembrane domain linker-intracellular domain. Exemplary recombinant antigen-binding domains i) and ii) are designated herein “cell binder” or “CB”. Exemplary recombinant antigen-binding domains iii) and iv) are designated herein “chimeric antigen receptor” or “CAR”. Preferably, the recombinant antigen binding domain is an antigen-binding domain of an antibody. Fusion polypeptide further comprising a transmembrane domain but devoid of a signaling intracellular domain In some embodiments, the fusion polypeptide comprising the recombinant antigen- binding domain (preferably an antigen-binding domain of an antibody) and a transmembrane domain is devoid of a signaling intracellular domain. This means that the fusion polypeptide may comprise an intracellular domain, provided that this intracellular domain does not have signaling activity, meaning that the binding of the antigen to the antigen-binding domain of the fusion polypeptide does not result in activation of signaling cascades. In this case, the fusion polypeptide is devoid of any signaling intracellular domain, so that it is devoid of a signaling intracellular stimulatory domain, and also devoid of a signaling intracellular co-stimulatory domain. Fusion polypeptide further comprising a transmembrane domain and a signaling intracellular domain In another embodiment, the fusion polypeptide comprises the recombinant antigen- binding domain (preferably an antigen-binding domain of an antibody), a transmembrane domain and a signaling intracellular domain. The fusion polypeptide then preferably comprises a signaling intracellular stimulatory domain. The fusion polypeptide comprising a signaling intracellular stimulatory domain may optionally further comprise a signaling intracellular co-stimulatory domain (one or more). In some embodiments, the fusion polypeptide comprises a signaling intracellular stimulatory domain, a first signaling intracellular co-stimulatory domain and a second signaling intracellular co-stimulatory domain, wherein the first and second signaling intracellular co-stimulatory domains are different. Preferably, the signaling intracellular stimulatory domain or the signaling intracellular co-stimulatory domain is from a molecule selected from the group consisting of TCR, CD3ζ, CD3γ, CD3δ, CD3ε, CD86, common FcγR, FcεR, CD79a, CD79b, FcγRIIa, FcβR, DAPIO, DAP 12, T cell receptor (TCR), CD27, CD28, 4-1BB (CD137), OX40, CD30, CD40, CD40L, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, KG2C, B7-H3, a ligand that specifically binds with CD83, CDS, ICAM-1, GITR, BAFFR, HVEM (LIGHTR), SLAMF7, Kp80 (KLRF1), CD127, CD160, CD19, CD4, CD8α, CD8β, IL2Rβ, IL2Rγ, IL7Rα, ITGA4, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CD11d, ITGAE, CD103, ITGAL, CD11a, LFA-1, ITGAM, CD11b, ITGAX, CD11c, ITGB1, CD29, ITGB2, CD 18, LFA-1, ITGB7, T FR2, TRANCE / RA KL, DNAM1 (CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (Tactile), CEACAM1, CRTAM, Ly9 (CD229), CD160 (BY55), PSGL1, CD100 (SEMA4D), CD69, SLAMF6 (NTB-A, Ly108), SLAM (SLAMF1, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, LAT, GADS, SLP-76, PAG / Cbp, Kp44, Kp30, Kp46, KG2D. More preferably: • the signaling intracellular stimulatory domain is from a molecule selected from the group consisting of a CD3ζ, FcγR, a FcβR, CD3γ, CD3δ, CD3ε, CDS and FcγRIIa; and • when present, the signaling intracellular co-stimulatory domain is from a molecule selected from the group consisting of CD28, 4-1BB, CD40L, ICOS, CD27, CD244 or OX40. Preferred genetically modified immune cells In a preferred embodiment, the genetically modified immune cell according to the invention comprises: i. a first recombinant polynucleotide, or a first vector comprising a first recombinant polynucleotide, wherein the first recombinant polynucleotide encodes a means for binding an antigen, preferably a recombinant antigen- binding domain as defined herein or a fusion polypeptide comprising a recombinant antigen-binding domain and a transmembrane domain (and optionally a non-signaling or a signaling intracellular domain) as defined herein, and a second recombinant polynucleotide, or a second vector comprising a second recombinant polynucleotide, wherein the second recombinant polynucleotide encodes a p21 protein, or ii. a recombinant polynucleotide, or a vector comprising recombinant polynucleotide, wherein the recombinant polynucleotide encodes (1) a means for binding an antigen, preferably a recombinant antigen-binding domain as defined herein or a fusion polypeptide comprising a recombinant antigen- binding domain and a transmembrane domain (and optionally a non-signaling or a signaling intracellular domain) as defined herein, and (2) a p21 protein. In such genetically modified immune cells, the first recombinant polynucleotide of i., the second recombinant polynucleotide of i., or the recombinant polynucleotide of ii. is preferably operably linked to a promoter chosen in the list consisting of EF1α (elongation factor 1α, and in particular EFS: elongation factor 1α short, a constitutive promoter), SFFV (silencing-prone spleen focus forming virus, a constitutive promoter), E2F1 (E2 promoter binding factor 1, a constitutive promoter), CMV (cytomegalovirus, a constitutive promoter), RSV (Rous sarcoma virus, a constitutive promoter), U6 (a constitutive promoter), UBC (Ubiquitin C, a constitutive promoter), SV40 (Simian Virus 40, a constitutive promoter), TRE (Tetracycline Response Element, an inducible promoter), and the like. Preferred recombinant polynucleotides and vectors and methods to transfer them into the immune cell Preferably, the recombinant polynucleotide encoding the polypeptide or fusion polypeptide of interest (a p21 protein; another protein, which overexpression results in upregulation of p21 protein expression; a means for binding an antigen, preferably a recombinant antigen-binding domain (preferably an antigen-binding domain of an antibody); or a fusion polypeptide comprising a recombinant antigen-binding domain (preferably an antigen-binding domain of an antibody), a transmembrane domain (optionally a hinge domain and a transmembrane domain), and optionally an intracellular non-signaling or signaling domain) is a synthetic polynucleotide, that is to say it is a polynucleotide from a synthetic source, for example produced by genetic engineering. In this context, the sequence of the mRNA encoding the polypeptide of interest may be optimized for the purpose of improving its stability and translatability, by methods and means known in the art such as for example the modification of rare codons (“also known as codon-optimization”) with synonymous frequently occurring codons, for increasing expression levels, or the modification of the 5’ mRNA cap with 5'-phosphorothiolate dinucleotide cap analogues, for inhibiting RNA decapping and improving resistance to enzymatic degradation, or the incorporation of base modified nucleosides to amplify the translation of mRNA in the cell (such as reviewed by Bornewasser L et al.). Preferred recombinant polynucleotides include mRNA, gDNA or cDNA molecules. Preferred vectors include viral vectors and non-viral vectors such as plasmids. The transfer of a recombinant polynucleotide or non-viral vector may be performed by any appropriate method known in the art, including electroporation, nanoparticles, lipid nanoparticles (LNP), cell penetrating peptides, zwitterionic amino lipids (ZALs, such as disclosed by Miller J.B. et al., 2017), polyplexes and polymeric micelles. LNP formulations are typically composed of (1) an ionizable or cationic lipid or polymeric material, bearing tertiary or quaternary amines to encapsulate the mRNA; (2) a zwitterionic lipid that resembles the lipids in the cell membrane (such as for instance 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine [DOPE]); (3) cholesterol to stabilize the lipid bilayer of the LNP; and (4) a polyethylene glycol (PEG)-lipid. Use of LNP to introduce in vitro transcribed mRNA with such technique was described for instance by Billingsley MM, et al., 2024. See also reviews such as Liu et al., Int. J. Mol. Sci. 2024, 25(18), 10166; Kularatne et al., Pharmaceuticals (Basel). 2022 Jul 20;15(7):897; Marques et al., Pharmaceutics. 2023 Jan 8;15(1):216; Xu and Xia, ACS Nanosci. Au. 2023;3:192–203. Various LNP formulations are known in the art that comprise ionizable cationic lipids (ICLs), phospholipids, cholesterol, and polyethylene glycol (PEG) lipids. LNPs can be used as a drug delivery platform for a variety of cargos, including small-molecule drugs, mRNA, proteins, or peptides. The core is formed by the combination of these cargos and lipid molecules through electrostatic or hydrophobic interactions. The shell is composed of lipids that encapsulate the core, and is frequently functionalized with auxiliary components that improve uptake and targeting of the LNPs. For example, the LNP can be functionalized with specific targeting ligands (such as antibodies, peptides, and glycans). Antibodies or antigen-binding domains can be conjugated to LNPs to enable high-affinity binding to cell-specific receptors, through chemical conjugation techniques known in the art. For example, amidation has been used to conjugate anti-CD34 antibody to DSPE-PEG- carboxyl. Thiol-maleimide conjugation has been used to conjugate anti-CD4 antibody and anti-PECAM-1 antibody to DSPE-PEG-maleimide containing LNP. Fab-C4 containing a cyclopentadiene lysine derivative has been conjugated to DSPE-PEG-maleimide via a Diels-Alder reaction. Alternatively, a targeting ligand can be attached to cholesterol instead of PEG-lipid. For example, α-mannose containing an aminopropyl succinate spacer has been conjugated to cholesterol via an amide bond and formulated into LNP to deliver saRNA to dendritic cells. Polyplexes are particles, usually spherical, made up from polymer molecules engaging in electrostatic interactions with negatively charged nucleic acids. They can be made of poly(ethyleneimine) (PEI), poly(amino acids) (such as P(Lys) or P(Asp)), polyesters (such as poly(lactic-co-glycolic acid), poly(^^-amino ester)s or poly(amine-co- ester)), natural polymers (Chitosan, Protamine) or poly(amidoamine) (PAMAM). For example, a viral vector is used for transfer into the immune cell of a recombinant polynucleotide encoding under the control of appropriate regulatory sequences a polypeptide of interest (a p21 protein; another protein, which overexpression results in upregulation of p21 protein expression; an antigen-binding domain; or a fusion polypeptide comprising an antigen-binding domain, a transmembrane domain, and optionally an intracellular non-signaling or signaling domain). Transfer can be in vivo or ex vivo. As another example, the LNP formulation is used for transfer into the immune cell, in vivo or ex vivo. In some embodiments, the immune cell is preferably infected with the viral vector under appropriate conditions for infection. Those skilled in the art will know appropriate conditions for infection (medium, temperature, multiplicity of infection…) depending on the immune cell and the type of virus. The Examples notably contain exemplary conditions for infection of monocytes using a replication-defective lentivirus. More preferably, the viral vector is any viral vector disclosed as appropriate in the section below relating to vectors according to the invention. Therefore, a genetically modified cell according to the invention preferably comprises any viral vector or combination of viral vectors disclosed as appropriate in the section below relating to vectors according to the invention. Cell population comprising genetically modified immune cells The present invention also relates to a cell population comprising genetically modified immune cells according to the invention. In the cell population, the genetically modified immune cells can be all the same (i.e. all the cells are derived from a single clone) or different. In the latter case, the genetically modified immune cells may express at their surface several distinct means for binding an antigen (preferably antigen-binding domains) or the same means for binding an antigen (preferably an antigen-binding domain). When the genetically modified immune cells express at their surface several distinct means for binding an antigen (preferably antigen-binding domains), the distinct means for binding an antigen (preferably antigen-binding domains) may bind to several distinct antigens (preferably several distinct cancer antigens, in particular selected from the group of preferred cancer antigens described herein) or to the same antigen, in which case they may bind to distinct or identical epitopes, provided that the means for binding an antigen (preferably antigen-binding domains) are distinct. When the genetically modified immune cells express at their surface the same means for binding an antigen (preferably an antigen-binding domain), they may still be distinct, for instance when the population has been obtained by transformation of a population of immune cells and the obtained cell population comprises several distinct clones comprising the same transformed recombinant polynucleotides or vectors. Vector(s) The present invention also relates to a vector, or a combination of at least two vectors (preferably two vectors), comprising: • a first polynucleotide encoding a means for binding an antigen, preferably a recombinant antigen-binding domain, or a fusion polypeptide comprising a recombinant antigen-binding domain (preferably an antigen-binding domain of an antibody) and a transmembrane domain, and • a second polynucleotide encoding a p21 protein. In some embodiments the invention relates to a bicistronic vector comprising (i) a first polynucleotide encoding a means for binding an antigen, preferably a recombinant antigen-binding domain, or a fusion polypeptide comprising a recombinant antigen- binding domain (preferably an antigen-binding domain of an antibody) and a transmembrane domain, and (ii) a second polynucleotide encoding a p21 protein. The use of a vector (e.g. plasmid, or virus) makes it possible to improve the administration of polynucleotides encoding polypeptides of interest in target immune cells, and also to increase the stability of said polynucleotides into said immune cells, thereby enabling a long-lasting effect to be obtained. Type of vector Both viral and non-viral vectors may be used. In some embodiments, a viral vector is used. More preferably, said viral vector is chosen in the group consisting of: adenovirus, adeno-associated virus (AAV), herpesvirus, lentivirus, vaccinia virus, cytomegalovirus (CMV) and the like, that have been shown to effectively transfect macrophages (Singh G. et al, F1000 research 2015). Advantageously, said virus is a replication-defective virus. AAV vectors display several advantages such as i) a long-lasting expression of synthesized genes, ii) a low risk for pathogenic reactions (because they are artificially manufactured and not toxic), iii) they trigger low immunogenic response and iv) they do not integrate the human genome. In order to increase the efficacy of gene expression, and prevent the unintended spread of the virus, genetic modifications of AAV can be performed. These genetic modifications include the deletion of the E1 region, deletion of the E1 region along with deletion of either the E2 or E4 region, or deletion of the entire adenovirus genome except the cis-acting inverted terminal repeats and a packaging signal. Such vectors are advantageously encompassed by the present invention. We can also use the non-viral Sleeping Beauty stable transposition of p21 gene from supercoiled minimal DNA vectors called minicircles. The genetic engineering of the monocytes could also be performed by the use of the non-viral transfer of in vitro transcribed p21 mRNA in the monocytes. The plasmids in these two methods are delivered by transfection of monocytes through electroporation. Another advantageous vector is an adenoviral vector. Indeed, Haddada H. et al. Biochem. Biophys. Res. Commun (1993) showed that adenoviruses are capable of very effectively infecting cells of the monocyte-macrophage line, of being maintained stably therein and of expressing a therapeutic gene. Different serotypes of adenovirus exist, the structure and properties of which vary somewhat but which are not pathogenic for man, and in particular for non-immunosuppressed subjects. Moreover, these viruses do not integrate in the genome of the cells they infect, and can incorporate large fragments of exogenous DNA. Among the different serotypes, it is preferable in the context of the present invention to use adenoviruses type 2 or 5 (Ad 2 or Ad 5). In the case of Ad 5 adenoviruses, the sequences needed for replication are the E1A and E1B regions. These sequences are preferable deleted from the recombinant nucleic acid used in the present invention. Another advantageous vector for the preparation of the cell compositions according to the invention is a lentivirus. Lentiviruses like HIV have the capacity to infect non- dividing and dividing cells and to integrate into the host cell genome. Due to these characteristics, HIV-based lentiviral vectors have been proposed as good delivery system candidates for gene therapy, but the attempt to use them in clinical trials has raised concerns about their safety including the risk of genetic recombination leading to the generation of replication-competent retrovirus in humans. Further modifications in the packaging and genetic components of viral genes have been carried out to develop safer HIV-based lentiviral vector systems. Today, a number of safe HIV-based lentiviral vectors have been designed for efficiently transducing target genes into differentiated monocyte- derived macrophages (Leyva F. et al, BMC biotechnology (2011). Any of these vectors can be used in the context of the present invention. Particularly preferred viral vectors in the context of the invention are lentiviral vectors, in particular replication-defective lentiviral vectors. Preferred lentiviral vectors are those that have been modified so as to be safely administered into mammals. These vectors are for example the HIV / SIV vectors known to be useful in human or mammal gene therapy, as disclosed in Neschadim A. et al. Biol Blood Marrow Transplant. 2007 Dec;13(12):1407-16. The most interesting vectors to use are the HIV and SIV based lentiviral Self Inactivating vectors (Neschadim A. et al. Biol Blood Marrow Transplant. 2007 Dec;13(12):1407-16.), the adenoviral vectors (Haddada H. et al. Biochem. Biophys. Res. Commun (1993)) and the sleeping Beauty transposon non- viral vectors (Aronovich et al. Human. Molecular. Genetics (2011)). Regulatory sequences controlling the expression of the polypeptide of interest In the vector or combination of vectors of the invention, the first polynucleotide encoding an antigen-binding domain or a fusion polypeptide comprising an antigen- binding domain and a transmembrane domain and the second polynucleotide encoding a p21 protein are preferably placed under the control of regulatory elements permitting the expression of the polypeptide of interest (the antigen-binding domain or fusion polypeptide and the p21 protein). These regulatory elements generally consist of transcription promoter sequences. These can be sequences which are naturally responsible for the expression of the polypeptide of interest, when these sequences are capable of functioning in monocytes-macrophages. They can also be sequences of different origin (responsible for the expression of other proteins, or even synthetic genes). In particular, they can be promoter sequences of eukaryotic or viral genes. For example, they can be promoter sequences originating from the genome of the immune cell that it is desired to infect. Similarly, they can be promoter sequences originating from the genome of a virus. In this connection, the promoters of EF1α (elongation factor 1α, and in particular EFS: elongation factor 1α short, a constitutive promoter), SFFV (silencing-prone spleen focus forming virus, a constitutive promoter), E2F1 (E2 promoter binding factor 1, a constitutive promoter),CMV (cytomegalovirus, a constitutive promoter), RSV (Rous sarcoma virus, a constitutive promoter), U6 (a constitutive promoter), UBC (Ubiquitin C, a constitutive promoter), SV40 (Simian Virus 40, a constitutive promoter), TRE (Tetracycline Response Element, an inducible promoter), and the like, may be mentioned for example. In addition, these expression sequences may be modified by the addition of activator sequences, regulatory sequences, and the like. The choice of the vector and of the regulatory sequences should be done by the skilled person keeping in mind that the final expression of the polypeptide of interest by the immune cells of the invention should be enhanced by at least two or three times as compared with mock-transfected control immune cells. Construction of the vector Methods to construct expression vectors containing coding sequences and appropriate transcriptional / translational control signals are well known in the art. These methods include, for example, in vitro recombinant DNA techniques, synthetic techniques and in vivo recombination / genetic recombination. The nucleic acids may be isolated and obtained in substantial purity, then introduced into suitable host cells using a variety of techniques available in the art. All the techniques of construction of vectors derived from adenoviruses, lentiviruses, or from AAV, and incorporation of heterologous nucleic acid sequences in same, have been described in the literature and can be used in the context of the present invention. The methods traditionally used in molecular biology, such as preparative extractions of plasmid DNA, centrifugation of plasmid DNA in a caesium chloride gradient, agarose or acrylamide gel electrophoresis, purification of DNA fragments by electroelution, phenol or phenol-chloroform extraction of proteins, ethanol or isopropanol precipitation of DNA in a saline medium, transformation in Escherichia coli, and the like, are well known to a person skilled in the art and are amply described in the literature [Maniatis T. et al., “Molecular Cloning, a Laboratory Manual”, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1982; Ausubel F. M. et al. (eds), “Current Protocols in Molecular Biology”, John Wiley & Sons, New York, 1987]. Once the genome of a virus has been genetically modified, the virus is multiplied and recovered and purified according to standard techniques of molecular biology. Exemplary techniques for generating appropriate replication-defective lentiviral vectors or combinations of vectors according to the invention are disclosed in the Examples. Preferred vectors or combinations of vectors In some embodiments, the vector is a bicistronic vector, such as a (preferably replication-defective) lentiviral vector, comprising a first polynucleotide encoding p21 protein (such as polynucleotide comprising or consisting of SEQ ID NO: 5) and a second polynucleotide encoding a recombinant antigen-binding domain, or a fusion polypeptide comprising an antigen-binding domain of interest (preferably an antigen-binding domain of an antibody)) and a transmembrane domain, wherein the antigen is: i) a tumor antigen; ii) a solid tumor antigen; iii) selected from the group consisting of CD19, HER2, GD2, OAcGD2, Nectin-4, Claudin 18.2, GPC3, MSLN, B7-H3, MUC1, CEA, EGFR, PSMA, EPCAM, EGFRVIII, ILI3RA2, CD133, CD47, CD24, MAGE-A4, TROP2, BCMA, CD22, CD7, CD30, CD20, CD123, CD38, CD33, CD138, CCL-1, SLAMF7, CD5, NKG2D ligands, NKG2D, CD79b, CD70, ROR1, FLT3, CD97, CD99 and CD18; or iv) selected from the group consisting of HER2, GD2, Nectin-4, Claudin 18.2. A particularly preferred vector is a bicistronic vector, such as a (preferably replication-defective) lentiviral vector, comprising SEQ ID NO: 9 encoding p21 protein and a chimeric antigen receptor specifically binding to HER2, or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO: 9 encoding p21 protein and a chimeric antigen receptor specifically binding to HER2. In another embodiment, the vector (e.g. a lentiviral vector) is a bicistronic vector comprising the nucleic acid sequence SEQ ID NO: 43 encoding encoding p21 protein and a HER2 specific cell binder, or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO:43 encoding encoding p21 protein and a HER2 specific cell binder. In an embodiment, the vector (e.g. a lentiviral vector) is a bicistronic vector comprising the nucleic acid sequence SEQ ID NO: 33 encoding encoding p21 protein and a chimeric antigen receptor specifically binding to GD2, or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO:33 encoding encoding p21 protein and a chimeric antigen receptor specifically binding to GD2. In an embodiment, the vector (e.g. a lentiviral vector) is a bicistronic vector comprising the nucleic acid sequence SEQ ID NO: 35 encoding encoding p21 protein and a cell binder specifically binding to GD2, or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO:35 encoding encoding p21 protein and a cell binder specifically binding to GD2. In an embodiment, the vector (e.g. a lentiviral vector) is a bicistronic vector comprising the nucleic acid sequence SEQ ID NO: 45 encoding encoding p21 protein and a chimeric antigen receptor specifically binding to Nectin-4, or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO:45 encoding encoding p21 protein and a chimeric antigen receptor specifically binding to Nectin-4. In an embodiment, the vector (e.g. a lentiviral vector) is a bicistronic vector comprising the nucleic acid sequence SEQ ID NO: 37 encoding encoding p21 protein and a cell binder specifically binding to Nectin-4, or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO:37 encoding encoding p21 protein and a cell binder specifically binding to Nectin-4. In an embodiment, the vector (e.g. a lentiviral vector) is a bicistronic vector comprising the nucleic acid sequence SEQ ID NO: 39 encoding encoding p21 protein and a chimeric antigen receptor specifically binding to Claudin 18.2, or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO:39 encoding encoding p21 protein and a chimeric antigen receptor specifically binding to Claudin 18.2. In an embodiment, the vector (e.g. a lentiviral vector) is a bicistronic vector comprising the nucleic acid sequence SEQ ID NO: 41 encoding encoding p21 protein and a cell binder specifically binding to Claudin 18.2, or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO:41 encoding encoding p21 protein and a cell binder specifically binding to Claudin 18.2. Another preferred embodiment is a combination of a first vector, such as a (preferably replication-defective) lentiviral vector, comprising SEQ ID NO: 5 encoding p21 protein or a nucleic acid sequence with at least 75%, preferably of at least 80%, at least 85%, more preferably of at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% identity with SEQ ID NO: 5 encoding p21 protein, and a second vector, such as a (preferably replication- defective) lentiviral vector, comprising a nucleotide sequence encoding a recombinant antigen-binding domain, or a fusion polypeptide comprising a recombinant antigen- binding domain of interest (preferably an antigen-binding domain of an antibody) and a transmembrane domain. In some embodiments, the second vector comprises a nucleotide sequence encoding a recombinant antigen-binding domain, or a fusion polypeptide comprising a recombinant antigen-binding domain of interest (preferably an antigen- binding domain of an antibody) and a transmembrane domain, wherein the antigen is: i) a tumor antigen; ii) a solid tumor antigen; iii) selected from the group consisting of CD19, HER2, GD2, OAcGD2, Nectin-4, Claudin 18.2, GPC3, MSLN, B7-H3, MUC1, CEA, EGFR, PSMA, EPCAM, EGFRVIII, ILI3RA2, CD133, CD47, CD24, MAGE-A4, TROP2, BCMA, CD22, CD7, CD30, CD20, CD123, CD38, CD33, CD138, CCL-1, SLAMF7, CD5, NKG2D ligands, NKG2D, CD79b, CD70, ROR1, FLT3, CD97, CD99 and CD18; or iv) selected from the group consisting of HER2, GD2, Nectin-4, Claudin 18.2. Methods for producing the genetically modified immune cell or cell population Genetically modified immune cells according to the invention or cell populations according to the invention may be produced in vitro and then administered to a subject for therapeutic uses or may be produced directly in vivo in a subject in need thereof. The present invention relates to a method of manufacturing a genetically modified immune cell (preferably in vitro) comprising transforming the immune cell with a recombinant polynucleotide encoding a p21 protein, wherein the immune cell already comprises a first recombinant polynucleotide encoding a recombinant antigen-binding domain. The present invention also relates to a method of manufacturing a genetically modified immune cell (preferably in vitro) comprising transforming the immune cell with a recombinant polynucleotide encoding an antigen-binding domain, wherein the immune cell overexpresses p21 protein. The present invention also relates to a method of manufacturing a genetically modified immune cell comprising modifying the immune cell to overexpress p21 protein, wherein the modifying is performed before or at the same time as transforming the immune cell with a recombinant polynucleotide encoding an antigen-binding domain. The present invention also relates to a method of manufacturing a genetically modified immune cell comprising modifying the immune cell to overexpress p21 protein, wherein the transforming is performed after or at the same time as transforming the immune cell with a recombinant polynucleotide encoding an antigen-binding domain. The present invention also relates to a method of manufacturing a genetically modified immune cell comprising: (a) modifying the immune cell to overexpress p21 protein and (b) modifying the immune cell to express a means for binding a cancer antigen, wherein (a) is conducted before, after or at the same time as (b). The present invention also relates to: a method of producing a genetically modified immune cell, wherein the immune cell is a monocyte, macrophage, dendritic cell or precursor thereof which expresses at its surface a recombinant antigen binding domain, the method comprising modifying the cell to overexpress p21 compared to a corresponding non-genetically modified immune cell. Means for overexpressing p21 CDKN1A gene, which encodes the p21 protein, is an endogenous gene in human immune cells. As a result, p21 overexpression can be obtained either by altering the endogenous CDKN1A gene in such a way that its expression is increased, or by transforming the immune cell with a recombinant polynucleotide or a vector comprising a recombinant polynucleotide, wherein the recombinant polynucleotide encodes a p21 protein. Alteration of the endogenous CDKN1A gene in order to increase endogenous p21 expression may include alteration of the regulatory sequences of the endogenous CDKN1A gene. For instance, the endogenous promoter may be mutated or replaced by a strong human or heterologous promoter suitable for expression in human cells. Alternatively, an enhancer sequence may be added in the CDKN1A gene. Another alternative would be to delete sequences of the CDKN1A gene binding to inhibitory transcription factors. Embodiments based on transformation of the immune cell with a recombinant polynucleotide or a vector comprising a recombinant polynucleotide, wherein the recombinant polynucleotide encodes a p21 protein, are described in more details below. Production of the genetically modified immune cell in vitro using transformation The present invention also relates to an in vitro method for producing a genetically modified immune cell according to the invention or a cell population according to the invention from a biological sample from a subject, comprising the step of transforming an immune cell or an immune cell population selected from monocytes, macrophages, dendritic cells and precursors or any of these cells from the biological sample with: a) a first recombinant polynucleotide or a first vector comprising a first recombinant polynucleotide, wherein the first recombinant polynucleotide encodes a means for binding an antigen, preferably a recombinant antigen-binding domain or a fusion polypeptide comprising a recombinant antigen-binding domain and a transmembrane domain, and a second recombinant polynucleotide or a second vector comprising a second recombinant polynucleotide, wherein the second recombinant polynucleotide encodes a p21 protein, or b) a recombinant polynucleotide or a vector comprising a recombinant polynucleotide, wherein the recombinant polynucleotide encodes (1) a means for binding an antigen, preferably a recombinant antigen-binding domain or a fusion polypeptide comprising a recombinant antigen-binding domain and a transmembrane domain, and (2) a p21 protein. The present invention also relates to an in vitro method for producing a genetically modified immune cell according to the invention, comprising transforming an immune cell (or a population of immune cells) selected from monocytes, macrophages, dendritic cells and precursors of any of these cells with: a) a first recombinant polynucleotide or a first vector comprising a first recombinant polynucleotide, wherein the first recombinant polynucleotide encodes a means for binding an antigen, preferably a recombinant antigen-binding domain or a fusion polypeptide comprising a recombinant antigen-binding domain and a transmembrane domain, and a second recombinant polynucleotide or a second vector comprising a second recombinant polynucleotide, wherein the second recombinant polynucleotide encodes a p21 protein, or b) a recombinant polynucleotide or a vector comprising a recombinant polynucleotide, wherein the recombinant polynucleotide encodes (1) a means for binding an antigen, preferably a recombinant antigen-binding domain or a fusion polypeptide comprising a recombinant antigen-binding domain and a transmembrane domain, and (2) a p21 protein. In a preferred embodiment, the biological sample comprises white blood cells, in particular monocytes, and is thus preferably chosen in the list consisting of whole blood, buffy coat (a fraction of an anticoagulated blood sample that contains most of the leukocytes and thrombocytes following centrifugation), peripheral blood mononuclear cells (PBMCs), white blood cells, and bone marrow. In a yet preferred embodiment, the biological sample is chosen in the list consisting of whole blood, buffy coat, PBMCs, and white blood cells. When the method comprises transforming a monocyte from the biological sample with a) a first recombinant polynucleotide or a first vector comprising a first recombinant polynucleotide, wherein the first recombinant polynucleotide encodes a means for binding an antigen, preferably a recombinant antigen-binding domain or a fusion polypeptide comprising a recombinant antigen-binding domain and a transmembrane domain, and a second recombinant polynucleotide or a second vector comprising a second recombinant polynucleotide, wherein the second recombinant polynucleotide encodes a p21 protein, the transformation with the first and second recombinant polynucleotides or vectors may be performed simultaneously in a single step, or separately in two distinct steps. In the latter case, any order of transformation with the first and second recombinant polynucleotides or vectors may be used (transformation with the first recombinant polynucleotide or vector followed by transformation with the second recombinant polynucleotide or vector, or the reverse). In addition, it is also possible to start from an immune cell already comprising the first recombinant polynucleotide or vector, or from an immune cell already comprising the second recombinant polynucleotide or vector. The present invention thus also relates to an in vitro method for producing a genetically modified immune cell according to the invention, comprising transforming an immune cell comprising a first recombinant polynucleotide or a first vector comprising a first recombinant polynucleotide, wherein the first recombinant polynucleotide encodes a means for binding an antigen, preferably a recombinant antigen-binding domain or a fusion polypeptide comprising a recombinant antigen-binding domain and a transmembrane domain, wherein the immune cell is a monocyte, a macrophage, a dendritic cell or a precursor of any of these cells, with a second recombinant polynucleotide or a second vector comprising a second recombinant polynucleotide, wherein the second recombinant polynucleotide encodes a p21 protein. The present invention also relates to an in vitro method for producing a genetically modified immune cell according to the invention, comprising transforming an immune cell comprising a second recombinant polynucleotide or a second vector comprising a second recombinant polynucleotide, wherein the second recombinant polynucleotide encodes a p21 protein, wherein the immune cell is a monocyte, a macrophage, a dendritic cell or a precursor of any of these cells, with a first recombinant polynucleotide or a first vector comprising a first recombinant polynucleotide, wherein the first recombinant polynucleotide encodes a means for binding an antigen, preferably a recombinant antigen-binding domain or a fusion polypeptide comprising a recombinant antigen-binding domain and a transmembrane domain. Transformation with the recombinant polynucleotide(s) or vector(s) can be performed by any appropriate method disclosed herein in the section “Preferred recombinant polynucleotides and vectors and methods to transfer them into the immune cell”. When using lentiviral vector(s), about 2 to 100 micrograms of lentiviral vector(s) may be used to transform about 10 millions of immune cells. Any of the above in vitro method for producing a genetically modified immune cell according to the invention may comprise one or more optional additional steps, as described below. When the genetically modified immune cell or cell population is intended to bind to a specific antigen of interest (in particular a cancer antigen, and preferably one of the preferred cancer antigens described herein), the method may further comprise a preliminary step of testing a population of antigen binding domains for binding to the antigen of interest and selecting an antigen-binding domain. A recombinant polynucleotide or a vector comprising a polynucleotide encoding the selected antigen- binding domain or a fusion polypeptide comprising the selected recombinant antigen- binding domain and a transmembrane domain is then used in the main transformation step of any in vitro method for producing a genetically modified immune cell according to the invention or a cell population according to the invention disclosed above. The present invention thus also relates to a method of manufacturing a genetically modified immune cell comprising (a) testing a population of antigen binding domains for binding to a cancer antigen, (b) selecting an antigen binding domain from step (a) and modifying an immune cell to express at its cell surface the selected antigen binding domain, and (c) modifying the immune cell to overexpress p21 protein, wherein step (b) is performed before, after or at the same time as step (c). Any in vitro method for producing a genetically modified immune cell according to the invention or a cell population according to the invention disclosed above may alternatively or further comprise a step of quantifying p21 expression (either at the protein or mRNA level) or SIRP-alpha downregulation in the transformed immune cell or cell population obtained after transformation. Any in vitro method for producing a genetically modified immune cell according to the invention or a cell population according to the invention disclosed above may alternatively or further comprise a step of cloning the transformed immune cell or cell population. Production of the genetically modified immune cell in vivo The present invention also relates to a method for producing a genetically modified immune cell according to the invention in a subject in vivo, comprising administering to the subject: a) a first heterologous polynucleotide, or a first vector comprising a first heterologous polynucleotide, wherein the first heterologous polynucleotide encodes a means for binding an antigen, preferably a recombinant antigen-binding domain, or a fusion polypeptide comprising an antigen-binding domain (preferably an antigen-binding domain of an antibody) and a transmembrane domain, and a second heterologous polynucleotide, or a second vector comprising a second heterologous polynucleotide, wherein the second heterologous polynucleotide encodes a p21 protein, or b) a heterologous polynucleotide, or a vector comprising a heterologous polynucleotide, wherein the heterologous polynucleotide encodes (1) a means for binding an antigen, preferably a recombinant antigen-binding domain, or a fusion polypeptide comprising a recombinant antigen-binding domain (preferably an antigen-binding domain of an antibody) and a transmembrane domain, and (2) a p21 protein. As used herein “heterologous polynucleotide” and “recombinant polynucleotide” are used interchangeably. Any appropriate method for transfer in vivo may be used. The recombinant polynucleotide(s) or vector(s) may preferably be designed so as to target the immune cell. The vector (lipid nanoparticles (LNP), cell penetrating peptides, zwitterionic amino lipids (ZALs, such as disclosed by Miller J.B. et al.), polyplexes, polymeric micelles, virus…) may notably contain a targeting moiety binding to the immune cell to which the recombinant polynucleotide(s) or vector(s) is (are) to be transferred. When the genetically modified immune cell is intended to bind to a specific antigen of interest (in particular a cancer antigen, and preferably one of the preferred cancer antigens described herein), the method may further comprise a preliminary step of testing a population of antigen binding domains for binding to the antigen of interest and selecting an antigen-binding domain. A recombinant polynucleotide or a vector comprising a polynucleotide encoding the selected antigen-binding domain or a fusion polypeptide comprising the selected antigen-binding domain and a transmembrane domain is then used in the main transformation step of any method for producing a genetically modified immune cell according to the invention in a subject in vivo disclosed above. Methods are known in the art for transfer in vivo in a subject in need thereof. For example, a subject with cancer or at risk of cancer is administered a vector or expression vector encoding (a) p21 and / or (b) the CAR or CB. The expression vector may be, for example, mRNA (e.g. as part of an LNP formulation), plasmid or viral vector. The vector may be part of a suitable pharmaceutical composition with appropriate pharmaceutically acceptable carrier(s). In some embodiments, the method comprises (a) producing a nanoparticle, optionally an LNP, comprising the expression vector(s) described herein encoding p21 and / or the CAR or CB, and (b) conjugating the nanoparticle, optionally an LNP, to an antibody or antigen-binding domain thereof that specifically binds a monocyte, a macrophage, a dendritic cell or a precursor of any of these cells. In some embodiments, the method further comprises detecting binding of an antibody or antigen-binding fragment to a suitable surface antigen prior to conjugating the nanoparticle to the antibody or antigen-binding domain. In some embodiments, a method of treating a subject with cancer or at risk of cancer comprises (a) producing an LNP comprising the expression vector(s) described herein encoding p21 and / or the CAR or CB, (b) conjugating LNP to an antibody or antigen- binding domain thereof that specifically binds a monocyte, a macrophage, a dendritic cell or a precursor of any of these cells, and (c) administering the LNP to the subject. In some embodiments, an LNP comprising the expression vector(s) described herein encoding p21 and / or the CAR or CB, and which is conjugated to an antibody or antigen- binding domain thereof that specifically binds a monocyte, a macrophage, a dendritic cell or a precursor of any of these cells, is for use for treating a subject with cancer or at risk of cancer. Surface antigens present on a monocyte, a macrophage, a dendritic cell or a precursor of any of these cells include BLTR1 (LTB4R), CCR2, CD11b, CD11c, CD132, CD14, CD16, CD163, CD18, CD29, CD305 (LAIR1), CD32a (FcγRIIA), CD33, CD36, CD38, CD4, CD4 / CCR5, CD45, CD46, CD47, CD64 (FcγRI), CD68, CR1 (CD35) , CR3 (CD11b / CD18), CX3CR1, CXCR3, CXCR4, DC-SIGN (CD209), Dectin-1 (CLEC7A), Dectin-2 (CLEC6A), HLA- DR, ICOSL (CD275), Langerin (CD207), LDLR (VSV-G), LOX-1 (OLR1), MDL-1 (CLEC5A), Mincle (CLEC4E), MR (CD206), PiT2 (SLC20A2), Siglec-1 (CD169), SIRPalpha, SR A1 (CD204), SR-A3 (MARCO), SR-A5, SR-A6 (SCARA6), TLR2, TLR2 / 1, TLR2 / 4, TLR2 / 4 + Dectin-1, TLR2 / 6, TLR3, TLR4, TLR4 / MD-2, and TLR5. With respect to the cell surface antigens described herein, the antibody or antigen- binding domain thereof, that specifically binds thereto may derive from antibodies that are available to the skilled person, including but not limited to: • CCR2: Plozalizumab (TAK-500), STX-0712, • CD11b: ASD14, • CD132: 2D4, BNZ-1 (peptide), • CD14: IC14 (Atibuclimab), • CD16: GMA161, IPH6101 / SAR443579, GTB-3650 TriKE®, • CD163: Zovostotug, • CD18: KIM-127, • CD29: OS2966, • CD32a (FcγRIIA): VIB9600, • CD33: Mylotarg, • CD36: PLT012, • CD38: Daratumumab, Isatuximab, • CD4: Ibalizumab, Semzuvolimab, Tregalizumab, Zanolimumab, • CD4 / CCR5: Leronlimab (PRO 140), • CD45: BC8, • CD46: FG-3246, • CD47: Magrolimab, • CR3: see CD11b / CD18, • CX3CR1: 455.1C11, • CXCR4: Ulocuplumab, • Dectin-2 (CLEC6A): BDC-3042, • HLA-DR: IMMU-114, • ICOSL (CD275): Prezalumab (MEDI-570), • LOX-1 (OLR1): Golocdacimab, • SIRPalpha: TTI-621, ALX148 (Evorpacept), Moflerafusp, Anzurstobart, Lumistobart, • SR-A3 (MARCO): Anti-MARCO mAb, • TLR2: Tomaralimab, and • TLR4: Paridiprubart. Method of testing a batch of genetically modified immune cells The present invention also relates to a method of testing a batch or population of genetically modified immune cells that (a) overexpress p21 protein and (b) express at the cell surface an antigen binding domain, comprising the step of detecting (and preferably quantifying) p21 protein or detecting (and preferably quantifying) a polynucleotide (mRNA) encoding p21 protein. As p21 overexpression results in SIRP-alpha downregulation, the present invention also relates to a method of testing a batch or population of genetically modified immune cells that (a) overexpress p21 protein and (b) express at the cell surface an antigen binding domain, comprising the step of detecting (and preferably quantifying) SIRP-alpha protein or detecting (and preferably quantifying) a polynucleotide encoding SIRP-alpha protein. The method may further comprise the step of detecting the expression of an antigen binding domain on the immune cell surface. Pharmaceutical compositions The present invention also relates to a pharmaceutical composition comprising: (a) a genetically modified immune cell according to the invention, or a vector, or combination of two vectors, according to the invention, and (b) a pharmaceutically acceptable excipient. Doses The pharmaceutical composition of the invention preferably comprises a therapeutically effective amount of a genetically modified immune cell according to the invention or a vector, or combination of two vectors, according to the invention. When the pharmaceutical composition of the invention comprises a genetically modified immune cell according to the invention, it may notably comprise between 1x109and 1x1010genetically modified immune cells. Excipients and administration forms In the context of the invention the pharmaceutically acceptable excipient can be solid, liquid, semisolid, or, in the case of an aerosol composition, gaseous. Non-limiting examples of pharmaceutically acceptable excipients include water, NaCI, normal saline solutions, lactated Ringer's, saccharide solution (e.g. glucose, trehalose, saccharose, dextrose, etc) alcohols, oils, gelatins, carbohydrates such as lactose, amylose or starch, fatty acid esters, hydroxymethycellulose, and the like as well as other aqueous physiologically balanced salt solutions may be used (see for example the most current edition of Remington: The Science and Practice of Pharmacy, A. Gennaro, Lippincott, Williams & Wilkins). Compositions for the treatment of cancer can usually be administered by parenteral, topical, intravenous, intratumoral, oral, subcutaneous, intraarterial, intracranial, intraperitoneal, intranasal or intramuscular means. A typical route of administration is intravenous or intratumoral, although other routes can be equally effective. For intravenous administration, the composition of the invention will be under liquid form. It will thus contain, apart from the cells, a pharmaceutically-acceptable diluent that does not affect the biological activity of the cells of the invention. Example of such diluents are physiological phosphate-buffered saline, Ringer's solutions, dextrose solution, and Hank's solution. In addition, the pharmaceutical composition or formulation may also include other carriers, adjuvants, or nontoxic, nontherapeutic, nonimmunogenic stabilizers and the like. In a preferred embodiment, the pharmaceutical composition of the invention is under a liquid form. Optional further active ingredient(s) The pharmaceutical compositions of the invention can further comprise another active principle (one or more), when combination of the genetically modified immune cell according to the invention or the vector, or combination of two vectors, according to the invention with another therapy is desired and simultaneous administration is appropriate. In particular, the pharmaceutical compositions of the invention can further comprise any other anticancer active principle that would not alter the genetically modified immune cell according to the invention or the vector or combination of two vectors according to the invention. The pharmaceutical composition of the invention can notably further comprise a therapeutically effective amount of a chemotherapeutic agent (preferably a chemotherapeutic agent that will not alter the genetically modified immune cell according to the invention, or the vector, or combination of two vectors, according to the invention), an agent that increases patient hematocrit, an immunotherapeutic agent, a hormone therapy agent (including notably compounds inhibiting hormone synthesis and antagonist of hormone receptors), an angiogenesis inhibitor, or any combination thereof. Exemplary chemotherapeutic agents include, but are not limited to, aldesleukin, altretamine, amifostine, asparaginase, bleomycin, capecitabine, carboplatin, carmustine, cladribine, cisapride, cisplatin, cyclophosphamide, cytarabine, dacarbazine (DTIC), dactinomycin, docetaxel, doxorubicin, dronabinol, duocarmycin, etoposide, filgrastim, fludarabine, fluorouracil, gemcitabine, granisetron, hydroxyurea, idarubicin, ifosfamide, interferon alpha, irinotecan, lansoprazole, levamisole, leucovorin, megestrol, mesna, methotrexate, metoclopramide, mitomycin, mitotane, mitoxantrone, omeprazole, ondansetron, paclitaxel (Taxol™), pilocarpine, prochloroperazine, saproin, tamoxifen, taxol, topotecan hydrochloride, vinblastine, vincristine and vinorelbine tartrate. Exemplary agents that increase patient hematocrit notably include erythropoietin stimulating agents (ESA). Such ESA are known and used in the art, including, for example, Aranesp® (darbepoetin alfa), Epogen®NF / Procrit®NF (epoetin alfa), Omontys® (peginesatide), Procrit®, etc. Exemplary immunotherapeutic agents include vaccines, anticancer antibodies and other anticancer cell therapies. Any vaccine that will not alter the genetically modified immune cell according to the invention or the vector or combination of two vectors according to the invention may further be present in the pharmaceutical composition. Anticancer antibodies include antibodies targeting an antigen expressed at the surface of cancer cells, which may induce antigen-binding dependent apoptosis, effector functions (such as antibody-dependent cell cytotoxicity (ADCC), phagocytosis, complement-dependent cell cytotoxicity), antibodies targeting angiogenesis, and immune checkpoint inhibitors. A number of antibodies are currently in clinical use for the treatment of cancer, and others are in varying stages of clinical development. For example, antibodies targeting an antigen expressed at the surface of cancer cells can be selected from anti-CD20 (mainly for the treatment of B cells malignancies, such as non-Hodgkin's lymphoma, for example rituximab, tositumomab, ibritumomab or ibritumomab tiuxétan), anti-CD52 (mainly for the treatment of chronic lymphocytic leukemia, such as alemtuzumab), anti-CD22 (mainly for the treatment of chemotherapy- resistant hairy cell leukemia), anti-CD33 (mainly for the treatment of acute myelogenous leukemia, such as Gemtuzumab), anti-EGFR (mainly for the treatment of colorectal and head / neck cancers, for example cetuximab and panitumumab), anti-HER2 (mainly for the treatment of breast and stomach cancers). Antibodies targeting angiogenesis may be selected from antibodies specifically binding to vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR, in particular VEGFR2), platelet-derived growth factor (PDGF), platelet- derived growth factor receptor (PDGFR, in particular PDGFRalpha), angiopoietin (Ang, in particular Ang-1 and Ang-2), Tie receptors, hepatocyte growth factor (HGF), and epidermal growth factor (EGF), Tyrosine-protein kinase Met (c-MET), and C-type domain family 14 member (CLEC14a). Exemplary immune checkpoint inhibitors (ICI) include anti-PD1 antibodies (such as Nivolumab or Pembrolizumab or Pidilizumab), anti-PD-L1 antibodies (such as Atezolizumab or Durvalumab), anti-CTLA-4 antibodies (such as Ipilimumab or Tremelimumab) anti-PD-L2 antibodies. Hormone therapy agents include notably hormones (like progestins) and hormone- blocking drugs (including compounds inhibiting hormone synthesis and antagonists of hormone receptors). Exemplary compounds inhibiting hormone synthesis include aromatase inhibitors (like letrozole, anastrozole exemestane and fulvestrant), CYP17 inhibitors (like abiraterone) and luteinizing hormone-releasing hormone (LHRH) agonists (such as goserelin or leuprolide). Exemplary antagonists of hormone receptors include selective estrogen receptor modulators (SERMs) (like tamoxifen, toremifene, raloxifene) and antiandrogens (like flutamide and bicalutamide). Angiogenesis inhibitors notably include antibodies targeting angiogenesis described above, but also chemical or biological drugs such as soluble VEGFR / VEGFR hybrids, and tyrosine kinase inhibitors. Therapeutic uses and methods The present invention also relates to the genetically modified immune cell according to the invention, the vector or combination of (at least) two vectors according to the invention, or the pharmaceutical composition according to the invention, for use as a medicament. The invention further relates to a method for treating a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the genetically modified immune cell according to the invention, the vector or combination of two vectors according to the invention, or the pharmaceutical composition according to the invention. Also provided is the genetically modified immune cell according to the invention, the vector or combination of (at least) two vectors according to the invention, or the pharmaceutical composition according to the invention, for the manufacture of a medicament for the treatment of a disease in a subject in need thereof. Indications The present invention also relates to the genetically modified immune cell according to the invention, the vector or combination of two vectors according to the invention, or the pharmaceutical composition according to the invention, for use in the treatment of a subject suffering from a cell proliferative disorder. The present invention also relates to the use of the genetically modified immune cell according to the invention, the vector or combination of two vectors according to the invention, or the pharmaceutical composition according to the invention for the manufacture of a medicament, preferably for treating a subject suffering from a cell proliferative disorder. The present invention also relates to the use of the genetically modified immune cell according to the invention, the vector or combination of two vectors according to the invention, or the pharmaceutical composition according to the invention for treating a subject suffering from a cell proliferative disorder. The present invention also relates to a method for treating a cell proliferative disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the genetically modified immune cell according to the invention, the vector or combination of two vectors according to the invention, or the pharmaceutical composition according to the invention. In preferred embodiments, the cell proliferative disorder is a tumour or a cancer. The present invention thus also relates to the genetically modified immune cell according to the invention, the vector or combination of two vectors according to the invention, or the pharmaceutical composition according to the invention, for use in the treatment of a subject suffering from a cancer. The present invention also relates to the use of the genetically modified immune cell according to the invention, the vector or combination of two vectors according to the invention, or the pharmaceutical composition according to the invention for the manufacture of a medicament, preferably for treating a subject suffering from a cancer. The present invention also relates to the use of the genetically modified immune cell according to the invention, the vector or combination of two vectors according to the invention, or the pharmaceutical composition according to the invention for treating a subject suffering from a cancer. The present invention also relates to a method for treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the genetically modified immune cell according to the invention, the vector or combination of two vectors according to the invention, or the pharmaceutical composition according to the invention. Treated cancers include both solid cancers and liquid cancers. In an embodiment, the cancer is a solid cancer. Examples of solid cancers include carcinoma (many subtypes), blastoma (including gliobastoma and neuroblastoma), sarcoma (including osteosarcoma), melanoma. More specific examples of solid cancers include squamous cell cancer (e.g. epithelial squamous cell cancer); lung cancer including small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung and squamous carcinoma of the lung; cancer of the peritoneum; liver cancer including hepatocellular cancer, hepatoma, hepatic carcinoma; gastric or stomach cancer including gastrointestinal cancer; pancreatic cancer (in particular pancreatic ductal adenocarcinoma); cervical cancer; ovarian cancer; head and neck cancer; cancers of the urinary tract, including bladder cancer, renal cancer (in particular renal carcinoma); breast cancer, including triple-negative breast cancer; colon cancer; rectal cancer; colorectal cancer; endometrial cancer, uterine cancer, salivary gland cancer; prostate cancer; vulval cancer; thyroid cancer; anal cancer; penile cancer; melanoma; brain cancers, including glioma, glioblastoma; and associated metastases. In another embodiment, the cancer is a liquid (also referred to as “haematological”) cancer, which refers to cancer that begins in blood-forming tissue, such as the bone marrow, or in the cells of the immune system. Examples of haematologic cancers are leukaemia (e.g., acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myelogenous leukaemia (CML), chronic lymphocytic leukaemia (CLL), or acute monocytic leukaemia (AMoL)), lymphoma (Hodgkin lymphoma or non-Hodgkin lymphoma), and myeloma (multiple myeloma, plasmacytoma, localised myeloma or extramedullary myeloma). In a preferred embodiment, the cancer is selected from the group consisting of pancreatic cancer (in particular pancreatic ductal adenocarcinoma); breast cancer, in particular triple negative breast cancer: ovarian cancer (in particular ovarian carcinoma); renal carcinoma; melanoma, gastric cancer, head and neck cancer, urothelial cancer, lung cancer, glioblastoma, neuroblastoma, and sarcoma (in particular osteosarcoma). The inventors have demonstrated that the invention is of particular interest in the treatment of cancers usually known to be difficult to treat, such as cancers presenting with tumors overexpressing CD47. The inventors have further demonstrated that the invention is particularly useful in the treatment of cancers resistant to radiation therapy and cancers sensitive to radiation therapy. However, treatment of cancers, in particular solid cancers, that do not overexpress CD47 is also within the scope of the invention as SIRPα was demonstrated to impair phagocytosis of solid cancer cells independently of CD47 expression (Huang, C. et al.., 2024). In an embodiment, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is thus for the treatment of a cancer overexpressing CD47. In an embodiment, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is for the treatment of a cancer presenting with tumors overexpressing CD47. In an embodiment, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is thus for the treatment of a cancer that does not overexpress CD47. In an embodiment, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is for the treatment of a cancer presenting with tumors that do not overexpress CD47. In another preferred embodiment, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is for the treatment of a cancer chosen from cancers resistant to radiation therapy and cancers sensitive to radiation therapy. A solid cancer resistant to radiation therapy may notably be selected from the group consisting of seminomas, medulloblastoma, neuroblastoma, Wilm’s tumor, early cervical carcinoma, and vaginal carcinoma. In a preferred embodiment, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is for the treatment of a cancer overexpressing a biological marker selected from the group consisting of Mre11-Rad50-Nbs1 complex, TRIP13, Ku80, BCL-2, BCL-XL, AKT, HIF- 1α, HIF-2α, CD73, PD-L1, CD47, HER2, GD2, Nectin-4, Claudin 18.2, and any combination thereof. In some embodiments the cancer overexpresses a biological marker selected from the group consisting of HER2, GD2, Nectin-4, and Claudin 18.2. In a yet preferred embodiment, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is for the treatment of a cancer overexpressing CD47, and optionally further one or more biological selected from the Mre11-Rad50-Nbs1 complex, TRIP13, Ku80, BCL- 2, BCL-XL, AKT, HIF-1α, HIF-2α, CD73, PD-L1, HER2, GD2, Nectin-4, and Claudin 18.2. In a preferred embodiment, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is for the treatment of a cancer overexpressing CD47, and further one or more biological selected from the Mre11-Rad50-Nbs1 complex, TRIP13, Ku80, BCL-2, BCL-XL, AKT, HIF- 1α, HIF-2α, CD73, PD-L1, HER2, GD2, Nectin-4, and Claudin 18.2. In some embodiments, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is for the treatment of a cancer overexpressing CD47, and further one or more of HER2, GD2, Nectin-4, and Claudin 18.2. Some types of cancers, listed below, are generally known in the art as more prone to developing or presenting with resistance to radiation therapy. In a preferred embodiment of the invention, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is for the treatment of a cancer selected from the group consisting of pancreatic cancer, in particular pancreatic ductal adenocarcinoma (PDAC), head and neck cancer, preferably head and neck squamous cell carcinoma, breast cancer, in particular triple-negative breast cancer (TNBC), prostate cancer, kidney cancer, lung cancer, preferably non-small cell lung cancer, and glioblastoma. Such cancers may present with one or more of the biological markers defined above, that is to say the biological markers of intrinsic or acquired resistance mechanisms involving the DNA damage response, tumor aneuploidy, the anti-apoptotic proteins such as BCL-2 and BCL-XL, the alteration of glucose metabolism pathway, hypoxia or the overexpression of negative immune modulators such as the ecto-5'-nucleotidase CD73, PD-L1 or CD47. In a preferred embodiment, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is for the treatment of a cancer selected from the group consisting of pancreatic cancer, in particular pancreatic ductal adenocarcinoma (PDAC), head and neck cancer, preferably head and neck squamous cell carcinoma, breast cancer, in particular triple-negative breast cancer (TNBC), prostate cancer, kidney cancer, lung cancer, preferably non-small cell lung cancer, and glioblastoma; and is a cancer overexpressing a biological marker selected from the Mre11-Rad50-Nbs1 complex, TRIP13, Ku80, BCL-2, BCL-XL, AKT, HIF- 1α, HIF-2α, CD73, PD-L1, CD47, HER2, GD2, Nectin-4, Claudin 18.2 and any combination thereof; preferably CD47 and optionally one or more biological marker selected from the Mre11-Rad50-Nbs1 complex, TRIP13, Ku80, BCL-2, BCL-XL, AKT, HIF-1α, HIF-2α, CD73, PD-L1, HER2, GD2, Nectin-4, and Claudin 18.2. In a preferred embodiment, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is for the treatment of pancreatic cancer, preferably pancreatic ductal adenocarcinoma (PDAC), and is a cancer overexpressing a biological marker selected from the Mre11- Rad50-Nbs1 complex, TRIP13, Ku80, BCL-2, BCL-XL, AKT, HIF-1α, HIF-2α, CD73, PD-L1, CD47, HER2, Nectin-4, Claudin 18.2 and any combination thereof; preferably CD47 and optionally one or more biological marker selected from the Mre11-Rad50-Nbs1 complex, TRIP13, Ku80, BCL-2, BCL-XL, AKT, HIF-1α, HIF-2α, CD73, PD-L1, HER2, Nectin-4, and Claudin 18.2. In a preferred embodiment, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is for the treatment of a cancer selected from the group consisting of pancreatic cancer, in particular pancreatic ductal adenocarcinoma (PDAC), head and neck cancer, preferably head and neck squamous cell carcinoma, breast cancer, in particular triple-negative breast cancer (TNBC), prostate cancer, kidney cancer, lung cancer, preferably non-small cell lung cancer, and glioblastoma and is a cancer overexpressing or not overexpressing CD47, and optionally one or more biological marker selected from the Mre11-Rad50-Nbs1 complex, TRIP13, Ku80, BCL-2, BCL-XL, AKT, HIF-1α, HIF-2α, CD73, PD-L1, HER2, GD2, Nectin-4, and Claudin 18.2. In a preferred embodiment, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is for the treatment of a cancer pancreatic cancer, preferably pancreatic ductal adenocarcinoma (PDAC), and is a cancer overexpressing, or not overexpressing, CD47, and optionally one or more biological marker selected from the Mre11-Rad50-Nbs1 complex, TRIP13, Ku80, BCL-2, BCL-XL, AKT, HIF-1α, HIF-2α, CD73, PD-L1, HER2, Nectin- 4, and Claudin 18.2. In some embodiments, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is for the treatment of a cancer overexpressing HER2, such as a bladder cancer, breast cancer, gastric / gastroesophageal cancer, gallbladder cancer, cholangiocarcinoma, cervical cancer, or ovarian cancer overexpressing HER2, and further overexpressing CD47, or not overexpressing CD47. In some embodiments, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is for the treatment a cancer overexpressing GD2, such as a glioblastoma, neuroblastoma, osteosarcoma, glioma, melanoma, lung cancer, in particular small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC), Ewing sarcoma, soft tissue sarcoma, retinoblastoma, breast cancer, or ovarian cancer overexpressing GD2, and further overexpressing CD47, or not overexpressing CD47. In some embodiments, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is for the treatment of a cancer overexpressing Nectin-4, such as a breast cancer, an ovarian cancer, a pancreatic cancer, a gastric cancer, a colorectal cancer, a bladder cancer, a non-small cell lung cancer (NSCLC), a hepatocellular carcinoma, a cholangiocarcinoma, a gallbladder cancer, a head and neck cancer, a renal cell cancer, or a urothelial cancer overexpressing Nectin-4, and further overexpressing CD47, or not overexpressing CD47. In some embodiments, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention is for the treatment of a cancer overexpressing Claudin 18.2, such as a gastroesophageal cancer, a pancreatic cancer, an ovarian mucinous tumour, a lung mucinous adenocarcinoma, or a cholangiocarcinoma overexpressing Claudin 18.2, and further overexpressing CD47, or not overexpressing CD47. Treated subject Usually, the treated subject will be a human, but non-human mammals may also be treated, e.g. companion animals such as dogs, cats, horses, etc., laboratory mammals such as rabbits, mice, rats, etc., and the like. The treated subject is thus a mammal preferably a human being. Preferably, the treated subject is a subject in need thereof, meaning that the subject is suffering or at risk of suffering from a cell proliferative disorder, in particular from any cancer described herein. A “subject in need thereof” is therefore a mammal, preferably a human being, that is suffering from cancer. Preferred therapeutic uses and methods A particular treatment use or method according to the invention comprises: (a) Isolating monocytes or their precursors (including pluripotent stem cells) from blood or bone marrow or umbilical cord, from the subject in need thereof or from a healthy donor, (b) Optionally, culturing their precursors so as to obtain a monocyte population, (c) Transforming the monocytes with a vector or a combination of vectors according to the invention encoding (1) an antigen-binding domain or a fusion polypeptide comprising an antigen-binding domain and a transmembrane domain and (2) a p21 protein, (d) Optionally, packaging and / or storing of the genetically modified monocytes thereby obtained, and (e) administering the genetically modified monocytes to the subject. Combinations with other therapies The genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention may be administered alone or combined with another anticancer therapy, such as another pharmaceutical composition or another active principle. Therefore, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention may be for use as a medicament, in particular in the prophylaxis or treatment of a cell proliferative disorder (in particular any cancer described herein), in combination with another anticancer therapy, such as a chemotherapy, an immunotherapy, a hormone therapy, an anti- angiogenesis therapy, a surgery or a radiotherapy. As used herein, the term “combined” does not imply that the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention and the other anticancer therapy (such as another pharmaceutical composition or another active principle) are necessarily administered simultaneously or in the same pharmaceutical composition. Combined use also extends to any use or presentation involving their administration at different time intervals, or in separate containers. Regarding time intervals, the genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition according to the invention and the other anticancer therapy may administered simultaneously (i.e. on the same day, either in a single pharmaceutical composition or in separate pharmaceutical compositions when using an active principle as combined therapy, depending on the compatibility of the two therapies and their administration routes) or non-simultaneously. In the latter case, when using an active principle as combined therapy, it is necessarily in a separate pharmaceutical composition. When administrations are non-simultaneous, they may be sequential (one therapy after the other in any order) or alternating (repeated administrations of both therapies, both necessarily with the same interval between two successive administrations). When repeated administrations of both therapies are needed, the repeated administrations will be considered simultaneous when they are systematically simultaneous, i.e. when the treatment starts with a simultaneous administration of both therapies and subsequent administrations are also simultaneous because both therapies are administered with the same interval between two successive administrations. When at least some administrations are non-simultaneous, the treatment will be considered are non-simultaneous administration (e.g. when both therapies have distinct intervals between two successive administrations and some doses are administered non-simultaneously but others may be simultaneous). The following examples merely intend to illustrate the present invention. EXAMPLES Example 1: Materials and Methods Primary cells and cell lines. Monocytes (herein abbreviated as “Mos”) were obtained from peripheral blood mononuclear cells (PBMCs) in the buffy coats of healthy donors from the French blood bank as previously described (Allouch, A. et al.). Briefly, Mos were isolated from PBMCs by adherence to plastic in macrophage medium (MM) (RPMI medium supplemented with 200 mM L-glutamine, 100 U / ml penicillin, 100 ^g / ml streptomycin, 10 mM HEPES, 10 mM sodium pyruvate, 50 ^M β-mercaptoethanol, 1% minimum essential medium vitamins and 1% nonessential amino acids; all from Gibco) containing 2% (vol / vol) heat inactivated (HI, 1 h at 56°C) human AB serum (hABS) (Sigma, #H3667). After extensive washing with DPBS (Gibco, #14190-094) to eliminate nonadherent cells, Mos were incubated overnight in MM containing 2% HI hABS and enriched using EasySep Human Monocyte Enrichment Kit without CD16 depletion (STEMCELL,#19058) before genetic engineering and differentiation into MDMs in 20% HI hSAB or mice adoptive transfer. Mo purity was analyzed by FACS and indicated 90 to 96% of cells expressed the markers hCD11b and hCD14 and did not express hCD56 (NK cells), hCD3 (T cells) and hCD20 (B cells). For differentiation into MDMs, engineered Mos were cultured for 6 to 7 days in MM containing 20% HI hABS in 96 wells plate (0.0625 x 106cells / well in triplicate) for killing assays, in 8 well chamber slides (0.25x106cells / well) for phagocytosis assays and in 24 wells plates (0.5 x 106cells) for qPCR or FACS analysis. The differentiated MDMs were adherent nonproliferating cells, among which 90-96% expressed macrophage (hCD11b, hCD14, hCD71) and M2-like (hCD163 and hCD206) markers. After differentiation MDMs were cultured in MM containing 10% HI FBS at 1x106 / ml. HS578T (#HBT-126, ATCC) and MDA- MB-468 (#300279, Cytion), SNU-601 (#305282, Cytion), SKOV3 (#HTB-77) and 4T1-Luc (4T1-Luc2, #CRL-2539-LUC2) cells were obtained from American Type Culture Collection (ATCC) and cultured in McCoy (Gibco, #36600021), DMEM (Gibco, #31966047), and RPMI (Gibco,#61870-10) medium supplemented with 10% HI FBS, respectively. TS / A cells (Sigma-Aldrich, #SCC177) were cultured in DMEM (Gibco, #31966047). SKOV3 and TS / A cell lines stably expressing luciferase gene were generated by the transfection of pLenti- CMV puro LUC (W168-1) plasmid (Addgene, #17477) and cultured with puromycin selection at the concentration 0.1 μg / ml and 1 μg / ml, respectively. TS / A-Luc and 4T1-Luc cell lines stably expressing HER2 gene were generated by the transfection of HER2 WT plasmid (Addgene, #16257) and cultured with neomycin (G418) selection at the concentration 500 μg / ml and 800 μg / ml, respectively. All target cells were confirmed to be negative for mycoplasma contamination and were cocultured for phagocytosis with MDMs in MM supplemented with 10% HI FBS. For in vitro and in vivo experiments, the puromycin and neomycin selections were removed three days before the phagocytosis assays or mice injections. Plasmids, lentiviral vectors and transduction. The sequence of human p21 corresponding to SEQ ID NO: 5 was subcloned in pAIP lentiviral vector plasmid. For specific HER2 assays, the sequence of E2F promoter-HER2CAR corresponding to SEQ ID NO: 31, and the sequence of p21-E2F promoter-CARHER2 corresponding to SEQ ID NO: 9, the sequence of E2F promoter-HER2CB corresponding to SEQ ID NO: 42, and the sequence of p21-E2F promoter-HER2CB corresponding to SEQ ID NO: 43 were subcloned in pAIP lentiviral vector plasmid. For specific GD2 assays, the sequence of E2F promoter-GD2CAR corresponding to SEQ ID NO: 32, the sequence of p21-E2F promoter-GD2CAR corresponding to SEQ ID NO: 33, the sequence of E2F1-GD2CB corresponding to SEQ ID NO: 34, and the sequence of p21-E2F promoter-GD2CB corresponding to SEQ ID NO: 35 were subcloned in pAIP lentiviral vector plasmid. For specific Nectin-4 assays, the sequence of E2F promoter-Nectin-4CAR corresponding to SEQ ID NO: 44, and the sequence of p21-E2F-Nectin-4CAR corresponding to SEQ ID NO: 45 the sequence of E2F promoter-Nectin-4CB corresponding to SEQ ID NO: 36, and the sequence of p21-E2F-Nectin-4CB corresponding to SEQ ID NO: 37 were subcloned in pAIP lentiviral vector plasmid. For specific CLDN18.2 assays, the sequence of E2F promoter-CLDN18.2CAR corresponding to SEQ ID NO: 38, the sequence of 21-E2F promoter-CLDN18.2CAR corresponding to SEQ ID NO: 39, the sequence of E2F promoter-CLDN18.2CB corresponding to SEQ ID NO: 40, the sequence of p21-E2F promoter-CLDN18.2CB corresponding to SEQ ID NO: 41 were subcloned in pAIP lentiviral vector plasmid The lentiviral and VLPs-Vpx productions were performed as previously described (Allouch, A. et al., 2022). The lentiviral vector quantifications for CAp24 content by ELISA were performed using RETROtek HIV-1 p24 Antigen ELISA 2.0 (ZeptoMetrix, #0801002) according manufacturer’s instructions. For the transductions, human Mos (107) were treated for 1 hour at 37°C with 1 ml VLPs-Vpx+containing 10 µg / ml polybrene (Sigma, #H9268) before the addition of 400 ng CAp24 of each control or / and encoding-gene lentiviral vectors with 10 µg / ml polybrene for overnight transduction in Opti-MEM medium (Gibco, #31985-070) (containing 2% HI FBS, 100 U / ml penicillin, 100 ^g / ml streptomycin). After extensive washings with medium, the Mos were resuspended in DPBS for the mice adoptive transfer or differentiated for 7 days in MM containing 20% HI hABS. The MDMs were cultured for at least two hours in MM containing 10% HI FBS (1x106 / ml) before additional experiments. RT-qPCR The RT-qPCR analysis of p21 expression in genetically engineered MDMs after 7 days differentiation and at least two hours culture in MM containing 10% HI FBS was performed as previously described (Allouch, A. et al., 2022). Flow cytometry analysis The analysis of SIRPα expression by flow cytometry determination of Mean Fluorescence Intensity (MFI) was performed as previously described (Allouch, A. et al., 2022). The binding assay of the of PE labeled HER2 recombinant protein bound to the CARHER2 expressed on the surface of genetically engineered MDMs was performed using the PE-labeled human Her2 / ErB2 protein, His tag (site specific conjugation) Kit (Accro Biosystems, #HE2-HPE3) according to manufacturer’s recommendations. Phagocytosis, proinflammatory activation and confocal microscopy The phagocytosis assays were performed in 8 well chamber slides (as previously described in Allouch, A. et al., 2022) with the ratio (1:1) of CMFDA stained genetically engineered MDMs (0.25 x 106) and CMTMR stained SKOV3, HS578T (#HBT-126, ATCC), MDA- MB-468 (#300279, Cytion) or SNU-601 (#305282, Cytion) cells. The proinflammatory activation of phagocytic MDMs was assessed with iNOS staining and confocal microscopy as previously described (Allouch, A. et al., 2022) at 72 hours after co-culture and after intracellular degradation of target cells. Cancer cell killing assay The cancer-killing assay was performed after co-culturing genetically engineered MDMs (0. 0625 x 106cells in triplicate each condition in 96 x wells) with solid tumor cells (0.032 x 106cells) expressing stably luciferase gene for 72 hours. The killing efficiency was determined by the luciferase activity normalized to control MDMs after cell lysis using the cell culture lysis reagent (Promega, #E153A) and the luciferase assay system Kit (Promega, #E1501) following manufacturer’s recommendations. Adoptive cellular transfer and ovarian cancer xenografts. Mouse studies were performed in accordance with protocols approved by the French Ethical Committee and following recommendations for proper use and care during animal experimentation. For tumor engraftment 8 to 10 weeks old-aged female NOD.Cg- PrkdcscidIl2rgtm1Wjl / SzJ (NSG) immunodeficient mice were intra-peritoneal injected with CD47+HER2+SKOV3-Luc cells (5x106). After 9 days mice were surveyed and randomized for tumor growth determined by bioluminescence radiance (p / s / cm2) using IVIS spectrum in vivo imaging system before the adoptive transfer of genetically engineered Mos (5 x 106cells / mouse) suspend in 200 ^l DPBS and injected intravenously in the tail. The tumor growths were followed with the bioluminescence activity. The ethical endpoints for mice sacrifice are the loss of 20% of body weight and / or clinical signs of illness. Statistics. Statistical analysis was performed with GraphPad Prism 8.0 (GraphPad). Statistical tests are indicated for each figure in the corresponding figure legend. For all figures, statistical significances are indicated as *p <0.05, **p <0.01, ***p<0.001, and ****p<0.0001. Results Engineering of human monocyte-derived macrophages for the expression of p21 and chimeric antigen receptor (CAR) or a cell binder specific for human epidermal growth factor receptor 2 (HER2) CAR macrophages were recently proposed as a novel therapeutic opportunity for the treatment of solid cancers (Klichinsky, M. et al). Macrophages expressing CAR for HER2 specifically targeted HER2 positive cancer cells (such as ovarian cancer cells) and enforced their internalization and destruction through phagocytosis (Klichinsky, M. et al). Considering their recent publication demonstrating that the overexpression of CDKN1A (p21) in macrophages transcriptionally represses the transcription of the phagocytosis inhibitor receptor SIRPα and unleashed the phagocytosis of CD47+ cancer cells (Allouch, A. et al), the inventors hypothesized that overcoming CD47- SIRPα phagocytosis checkpoint through p21-mediated transcriptional repression of SIRPα should enhance the phagocytosis and the removal of HER2+CD47+ solid cancer cells by macrophages expressing HER2-specific CAR or CB. Bicistronic lentiviral vectors encoding for control (Co.), human p21 (p21), HER2- specific CAR (HER2CAR), and HER2-specific CAR and p21 (HER2CAR / p21), HER2-specific CB (HER2CB), and HER2-specific CB and p21 (HER2CB / p21) were designed (Fig. 1a, Fig. 6a). Lentiviral construct used for the design of novel bicistronic lentiviral vectors for HER2CAR transduction contains anti-HER2 single chain variable fragment (scFv) (4D5), CD8α Hinge domain (HD), CD8α transmembrane domain (TM) and CD3ζ intracellular domain (ICD), as previously described (Klichinsky, M. et al). Lentiviral construct used for the design of novel bicistronic lentiviral vectors for HER2CB transduction contains anti- HER2 single chain variable fragment (scFv) (4D5), CD8α Hinge domain (HD), and CD8α transmembrane domain (TM). Human Mos were transduced with bicistronic lentiviral constructs (Fig. 1a-d, Fig. 6a-d) or co-transduced with lentiviral constructs expressing p21 or HER2CAR (HER2CAR + p21) (Fig. 1a,e) or p21 or HER2CB (HER2CB + p21) (Fig.6a-d). After 7-day differentiation, mRNA expression of p21 in transduced MDMs was analyzed using quantitative PCR, as previously described (Allouch, A. et al). A significant increase of p21 expression level was detected after transduction with p21, HER2CAR / p21 and HER2CAR + p21 lentiviral vectors (Fig.1b,d,e). No modulation of p21 expression level was detected after transduction with HER2CAR alone (Fig. 1c). Surprisingly, macrophages that were differentiated from Mos transduced with bicistronic lentiviral vector encoding for HER2CAR and p21 expression showed a huge increase of p21 mRNA expression level (Fig. 1d), as compared to MDMs engineered for p21 alone (Fig.1b) or MDMs co-transduced for HER2 CAR and p21 (HER2CAR + p21) expression (Fig. 1e). Then, SIRPα membrane expression was determined on engineered MDMs after 15 days using flow cytometry, as previously described (Allouch, A. et al). As expected, SIRPα membrane expression was found significantly reduced after transduction of p21, HER2CAR / p21 and HER2CAR + p21 lentiviral vectors (Fig. 1f) and inversely correlated with the increased expression of p21 mRNA level (Fig. 1b,d,e). The binding specificity of engineered MDMs for HER2 was then assessed using phycoerythrin (PE)-labeled recombinant HER2 protein and flow cytometry analysis. MDMs engineered for CARHER2 alone or CARHER2 and p21 expressed at their membrane a functional CAR that specifically recognized HER2 (Fig. 1g,h). Altogether, these results demonstrated that the cells manufactured according to the above were human MDMs expressing HER2CAR and repressing SIRPα expression. Increased expression of p21 enhances the phagocytosis of HER2+CD47+solid cancer cells by CAR macrophages. To assess the ability of engineered MDMs to engulf and eliminate HER2+CD47+solid cancer cells, control MDMs or MDMs expressing p21 and / or HER2CAR we then co-cultured with HER2+CD47+SKOV3 ovarian cancer cells and the percentage of MDMs showing tumor phagocytosis and poly-phagocytosis was determined using fluorescence microscopy and as previously described (Allouch, A. et al), at different time points (Fig.2a-c). During co- cultures of engineered MDMs with SKOV3 cells, a strong phagocytic activity of MDMs expressing both p21 and HER2CAR was detected after 10 minutes of co-cultures and reached a peak after 2 hours. After 10 minutes of co-culture, p21- or HER2CAR MDMs alone did not show significant increase of their phagocytic activity (Fig. 2b,c). A similar increase of phagocytic activities of p21- or HER2CAR-expressing MDMs was detected after 30 minutes of co-cultures (Fig. 2b), as compared to control macrophages. More importantly, a significant increase of phagocytosis was detected during co-culture of SKOV3 cells with MDMs expressing both p21 and HER2CAR, as compared to co-cultures of SKOV3 cells with p21- or HER2CAR-expressing MDMs (Fig. 2b), thus revealing that the simultaneous expression of p21 and HER2CAR on MDMs strongly enhances the phagocytosis of HER2+CD47+SKOV3 cells. Interestingly, poly-phagocytosis was detected during co-cultures of SKOV3 cells with MDMs expressing both p21 and HER2CAR (Fig. 2c). These results demonstrate that the overexpression of p21 and CAR HER2 on the membrane of MDMs strongly stimulate the internalization of HER2+CD47+cancer cells. We then determined effects of these processes on the removal of HER2+CD47+cancer cells. Human HER2+CD47+SKOV3 cells (Fig. 3a), and murine breast cancer cells (triple negative breast cancer 4T1 cells and mammary adenocarcinoma TS / A cells) overexpressing stably HER2 and firefly luciferase gene (Fig. 3b, c) were co-cultured with engineered MDMs and evaluate for luciferase activity. This strategy, which indirectly measures cytotoxic activities of engineered MDMs, revealed that human and murine MDMs expressing p21 or HER2CAR led to the removal of HER2+CD47+SKOV3 cells (Fig. 3d), HER2+CD47+4T1 cells (Fig. 3e) and HER2+CD47+TS / A cells (Fig. 3f) after 72 hours of co-culture. Interestingly, co-cultures of HER2CAR+p21+MDMs with target cells (Fig. 3d-f) enhanced the ability of HER2CAR+MDMs to eliminate HER2+cancer cells. Altogether, these results revealed that p21 overexpression enhances the ability of CAR-expressing MDMs to eliminate cancer cells. p21 / CARHER2-expressing MDMs exhibit an enhanced ability to undergo proinflammatory activation We then evaluated the ability of engineered MDMs to undergo proinflammatory activation after tumor phagocytosis, as previously published (Allouch, A. et al.), and observed using confocal microscopy and after 72 hours of co-culture, that p21- or HER2CAR-engineered MDMs showed an increased expression of inducible nitric oxide synthase (iNOS) (Fig. 4a,b). These results indicated that after tumor phagocytosis, p21+or HER2CAR+MDMs underwent proinflammatory activation. Interestingly, MDMs engineered for simultaneous expression of p21 and HER2-specific CAR revealed a significant increase of iNOS expression, as compared to p21+or HER2CAR+MDMs (Fig. 4a,b). Altogether, these results demonstrated the enhanced ability of HER2CAR+p21+MDMs to undergo proinflammatory activation as a consequence of increased tumor phagocytosis. Adoptive transfer of human Mos engineered for p21 and HER2CAR or HER2CB expression strongly support tumor regression and increased survival of infused mice We then evaluated the antitumor activity of HER2CAR / p21- or HER2CB / p21- induced, phagocytosis-guided cell therapy using mouse NOD.Cg-PrkdcscidIl2rgtm1Wjl / SzJ (NSG) bearing HER2+established tumors (Klichinsky, M. et al.). Control and NSG mice with intraperitoneal carcinomatosis (obtained after injection of luciferase-expressing HER2+SKOV3 cells) were intravenously infused with human control Mos or overexpressing p21, HER2CAR, HER2CAR / p21, HER2CB, or HER2CB / p21. Tumor growths were determined using IVIS spectrum in vivo imaging system (Fig. 5a). The adoptive transfer of p21+-or HER2CAR+p21+-expressing human Mos significantly delayed or stopped tumor growth in infused mice (Fig. 5b,c, Fig. 6b,c), as compared to mice infused with control or HER2CAR+human Mos. Accordingly, significant increases of survival were observed after infusion of mice with p21+or HER2CAR+p21+human Mos (Fig. 5d, Fig.6d), as compared to mice adoptively transferred with control or HER2CAR+mice. Interestingly, complete tumor regressions (3 / 10 and 5 / 10) were observed after infusions with p21+or HER2CAR+p21+human Mos, thus demonstrating that the adoptive transfer of HER2CAR+p21+human Mos into tumor-bearing mice reduces tumor growth more efficiently than those of HER2CAR+or p21+expressing human Mos. Similarly, the adoptive transfer of p21+-or HER2CB+p21+-expressing human Mos significantly delayed or stopped tumor growth in infused mice (Fig. 6b,c), as compared to mice infused with control or HER2CB+human Mos. Accordingly, significant increases of survival were observed after infusion of mice with p21+or HER2CB+p21+human Mos (Fig. 6d), as compared to mice adoptively transferred with control or HER2CB+mice. Engineering of human monocyte-derived macrophages for the expression of p21 and a chimeric antigen receptor (CAR) or a cell binder specific for ganglioside GD2, human nectin-4 (NECT4) or claudin 18.2 (CLDN18.2) The above experiments with macrophages expressing CAR or CB for HER2 were further extended to other tumor-specific antigens (GD2, Nectin-4 and Claudin 18.2) to demonstrate that p21-mediated transcriptional repression of SIRPα enhances the phagocytosis and the removal of CD47+solid cancer cells by macrophages expressing tumor-specific CARs or CBs. Bicistronic lentiviral vectors encoding for control (Co.) (Fig. 7a, Fig. 9a, Fig. 11a), human p21 (p21) (Fig. 7a, Fig. 9a, Fig. 11a), GD2-specific CAR (GD2CAR) (Fig. 7a), GD2- specific CAR and p21 (GD2CAR / p21) (Fig. 7a), GD2-specific CB (GD2CB) (Fig. 7a), GD2- specific CB and p21 (GD2CB / p21) (Fig. 7a), Nectin-4-specific CAR (NECT4CAR) (Fig. 9a), Nectin-4-specific CAR and p21 (NECT4CAR / p21) (Fig. 9a), Nectin-4-specific CB (NECT4CB) (Fig. 9a), Nectin-4-specific CB and p21 (NECT4CB / p21) (Fig. 9a), Claudin 18.2-specific CAR (CLDN18.2CAR) (Fig. 11a), Claudin 18.2-specific CAR and p21 (CLDN18.2CAR / p21) (Fig.11a), Claudin 18.2-specific CB (CLDN18.2CB) (Fig.11a), Claudin 18.2-specific CB and p21 (CLDN18.2CB / p21) (Fig. 11a) were designed. Human Mo were transduced with bicistronic lentiviral constructs (Fig. 7-11). After 7-day differentiation, percentages of MDMs expressing p21 after transfection MDMs were analyzed using fluorescent microscopy, as previously described (Allouch, A. et al. 2022). Significant increases of p21 expression levels were detected after transduction with p21, GD2CAR / p21, GD2CB / p21, NECT4CAR / p21, NECT4CB / p21, CLDN18.2CAR / p21 and CLDN18.2CB / p21 lentiviral vectors (Fig. 7b, 9b, and 11b). No modulation of p21 expression level was detected after transduction with GD2CAR, GD2CB, NECT4CAR, NECT4CB, CLDN18.2CAR or CLDN18.2 CB alone (Fig.7b, 9b and 11b), thus confirming our ability to efficiently transduce MDMs with these lentiviral constructs. Conclusions The results discussed above, supported by the figures, demonstrate that human macrophages, which were differentiated from Mos after lentiviral transduction for HER2- specific CAR and / or p21 expression, exhibit enhanced abilities for HER2+CD47+ cancer cell phagocytosis and for proinflammatory activation after tumor phagocytosis. The adoptive transfer of human Mos engineered for p21 and HER2CAR or HER2CB expression into mouse NOD.Cg-PrkdcscidIl2rgtm1Wjl / SzJ (NSG) bearing HER2+ established tumors reveals a greater antitumor efficacy and a significant increase of survival than mice infused with HER2CAR- or p21-expressing human Mos. Remarkably, more than half of mice infused with human Mo expressing p21 and a synthetic tumor-specific binder (HER2CAR or HER2CB) show complete tumor regression. Similarly, human macrophages differentiated from Mo after lentiviral transduction for p21 and / or as synthetic binder specific for ganglioside GD2, Nectin-4 or Claudin 18.2 tumor antigen, exhibit enhanced phagocytic abilities toward cancer cells expressing CD47 and tumor-associated antigens. Tumor phagocytosis is further shown to promote a heightened proinflammatory activation in these macrophages. These results demonstrate that the adoptive transfer of human Mos armored for synthetic tumor-specific binder and p21 expression is a promising strategy that could overcome several limitations encountered by current T cell immunotherapies (such as solid tumor homing and penetration, immunosuppressive microenvironment and antigen escape) and could improve efficacy of myeloid cell immunotherapies for solid cancers. BIBLIOGRAPHIC REFERENCES Allouch, A. et al. CDKN1A is a target for phagocytosis-mediated cellular immunotherapy in acute leukemia. 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Claims

CLAIMS 1. A genetically modified immune cell, which: (a) overexpresses p21 compared to a corresponding non-genetically modified immune cell, (b) expresses at its surface a recombinant antigen-binding domain, and (c) is a monocyte, a macrophage, a dendritic cell or a precursor any of these cells.

2. The genetically modified immune cell of claim 1, wherein the recombinant antigen- binding domain binds specifically to a tumor antigen.

3. The genetically modified immune cell of claim 1 or 2, wherein the recombinant antigen-binding domain is binds specifically to an antigen selected from the group consisting of CD19, HER2, GD2, OAcGD2, Nectin-4, Claudin 18.2, GPC3, MSLN, B7-H3, MUC1, CEA, EGFR, PSMA, EPCAM, EGFRVIII, ILI3RA2, CD133, CD47, CD24, MAGE-A4, TROP2, BCMA, CD22, CD7, CD30, CD20, CD123, CD38, CD33, CD138, CCL-1, SLAMF7, CD5, NKG2D ligands, NKG2D, CD79b, CD70, ROR1, FLT3, CD97, CD99 and CD18.

4. The genetically modified immune cell of any one of claims 1 to 3, wherein the recombinant antigen-binding domain comprises an antigen-binding domain of an antibody.

5. The genetically modified immune cell of any one of claims 1 to 4, wherein the recombinant antigen-binding domain is part of a fusion polypeptide further comprising a transmembrane domain.

6. The genetically modified immune cell of claim 5, wherein the fusion polypeptide comprises the recombinant antigen-binding domain fused to the transmembrane domain, optionally by a linker.

7. The genetically modified immune cell of claim 4, wherein the recombinant antigen- binding domain is part of a fusion polypeptide further comprising a hinge domain and a transmembrane domain.

8. The genetically modified immune cell of claim 7, wherein the fusion polypeptide comprises the recombinant antigen-binding domain fused to the hinge domain and transmembrane domain, optionally by a linker.

9. The genetically modified immune cell of any one of claims 5 to 8, wherein the transmembrane domain comprises a transmembrane region from a molecule selected from the group consisting of the alpha, beta or zeta chain of the T-cell receptor, CD28, CD3ε, CD45, CD4, CD5, CD8, CD9, CD 16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, CD154, Toll-like receptor 1 (TLR1), TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, and TLR9.

10. The genetically modified immune cell of any one of claims 7 to 9, wherein the hinge domain is a hinge domain of a molecule selected from the group consisting of the alpha, beta or zeta chain of the T-cell receptor, CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137 and CD154.

11. The genetically modified immune cell of any one of claims 5 to 10, wherein the fusion polypeptide is devoid of a signaling intracellular stimulatory domain, and devoid of a signaling intracellular co-stimulatory domain.

12. The genetically modified immune cell of any one of claims 5 to 10, wherein the fusion polypeptide further comprises a signaling intracellular stimulatory domain, and optionally a signaling intracellular co-stimulatory domain.

13. The genetically modified immune cell of any one of claims 1 to 12, wherein it comprises: i. a first recombinant polynucleotide, or a first vector comprising a first recombinant polynucleotide, wherein the first recombinant polynucleotide encodes the recombinant antigen-binding domain according to any one of claims 1 to 4 or the fusion polypeptide according to any one of claims 5 to 12, and a second recombinant polynucleotide, or a second vector comprising a second recombinant polynucleotide, wherein the second recombinant polynucleotide encodes a p21 protein, or ii. a recombinant polynucleotide, or a vector comprising recombinant polynucleotide, wherein the recombinant polynucleotide encodes (1) the recombinant antigen-binding domain according to any one of claims 1 to 4 orthe fusion polypeptide according to any one of claims 5 to 12, and (2) a p21 protein.

14. The genetically modified immune cell of claim 10, wherein the first recombinant polynucleotide of i., the second recombinant polynucleotide of i., or the recombinant polynucleotide of ii. is operably linked to a promoter chosen in the list consisting of the promoters of SFFV, EF1α, E2F1, CMV, U6, UBC, SV40, RSV and TRE.

15. A vector, or a combination of two vectors, comprising: - a first polynucleotide encoding the recombinant antigen-binding domain according to any one of claims 1 to 4, or the fusion polypeptide according to any one of claims 5 to 12, and - a second polynucleotide encoding a p21 protein.

16. The vector, or a combination of two vectors of claim 15, which is a bicistronic vector comprising (i) a first polynucleotide encoding the recombinant antigen-binding domain according to any one of claims 1 to 5, or the fusion polypeptide according to any one of claims 5 to 12, and (ii) a second polynucleotide encoding a p21 protein.

17. The vector, or a combination of two vectors of claim 15 or 16, wherein the antigen is: i) a tumor antigen; ii) a solid tumor antigen; iii) selected from the group consisting of CD19, HER2, GD2, OAcGD2, Nectin-4, Claudin 18.2, GPC3, MSLN, B7-H3, MUC1, CEA, EGFR, PSMA, EPCAM, EGFRVIII, ILI3RA2, CD133, CD47, CD24, MAGE-A4, TROP2, BCMA, CD22, CD7, CD30, CD20, CD123, CD38, CD33, CD138, CCL-1, SLAMF7, CD5, NKG2D ligands, NKG2D, CD79b, CD70, ROR1, FLT3, CD97, CD99 and CD18; or iv) selected from the group consisting of HER2, GD2, Nectin-4, Claudin 18.

2.

18. An in vitro method for producing a genetically modified immune cell as defined in any one of claims 1 to 14 from a biological sample from a subject, comprising:(a) transforming an immune cell or an immune cell population selected from monocytes, macrophages, dendritic cells and precursors or any of these cells from the biological sample of the subject, with: i. a first recombinant polynucleotide, or a first vector comprising a first recombinant polynucleotide, wherein the first recombinant polynucleotide encodes the recombinant antigen-binding domain according to any one of claims 1 to 4, or the fusion polypeptide according to any one of claims 5 to 12, and a second recombinant polynucleotide or a second vector comprising a second recombinant polynucleotide, wherein the second recombinant polynucleotide encodes a p21 protein, or ii. a recombinant polynucleotide or a vector comprising a recombinant polynucleotide, wherein the recombinant polynucleotide encodes (1) the recombinant antigen-binding domain according to any one of claims 1 to 4 or the fusion polypeptide according to any one of claims 5 to 12, and (2) a p21 protein.

19. A pharmaceutical composition comprising the genetically modified immune cell according to any one of claims 1 to 14, or the vector or the combination of two vectors according to any one of claims 15 to 17, and a pharmaceutically acceptable excipient.

20. The genetically modified immune cell according to any one of claims 1 to 14, the vector or the combination of two vectors according to any one of claims 15 to 17, or the pharmaceutical composition according to claim 19, for use as a medicament.

21. The genetically modified immune cell according to any one of claims 1 to 14, the vector or the combination of two vectors according to any one of claims 15 to 17, or the pharmaceutical composition according to claim 19, for use in the treatment of a subject suffering from a cell proliferative disorder.

22. The genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition for use according to claim 21, wherein said cell proliferative disorder is a cancer, preferably a solid cancer selected from the group consisting of pancreatic cancer, in particular pancreatic ductal adenocarcinoma; breast cancer, in particular triple negative breast cancer; ovarian cancer (in particular ovarian carcinoma), melanoma, gastric cancer, head and neck cancer, urothelialcancer, lung cancer, glioblastoma, neuroblastoma, and sarcoma (in particular osteosarcoma).

23. The genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition for use according to claim 21 or 22, wherein the use is for the treatment of a cancer chosen from cancers resistant to radiation therapy and cancers sensitive to radiation therapy.

24. The genetically modified immune cell, the vector or combination of two vectors or the pharmaceutical composition for use according to any one of claims 21 to 23, in combination with a chemotherapy, an immunotherapy, a hormone therapy, an anti- angiogenesis therapy, or a radiotherapy.

25. A method for treating a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the genetically modified immune cell according to any one of claims 1 to 14, the vector or combination of two vectors according to any one of claims 15 to 17, or the pharmaceutical composition according to claim 19.

26. The method of claim 25, wherein the subject is suffering from a cell proliferative disorder.

27. The method of claim 25, wherein said cell proliferative disorder is a cancer, preferably a solid cancer selected from the group consisting of pancreatic cancer, in particular pancreatic ductal adenocarcinoma; breast cancer, in particular triple negative breast cancer; ovarian cancer (in particular ovarian carcinoma), melanoma, gastric cancer, head and neck cancer, urothelial cancer, lung cancer, glioblastoma, neuroblastoma, and sarcoma (in particular osteosarcoma).

28. The method of claim 25, wherein the cancer is chosen from cancers resistant to radiation therapy and cancers sensitive to radiation therapy.

29. The method of any one of claims 25 to 28, wherein the genetically modified immune cell, the vector or combination of two vectors, or the pharmaceutical composition is administered in combination with a chemotherapy, an immunotherapy, a hormone therapy, an anti-angiogenesis therapy, or a radiotherapy.

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