19 results about "Atezolizumab" patented technology

The invention provides methods for classifying lung cancer (e.g., small cell lung cancer (SCLC), e.g., extensive stage SCLC (ES-SCLC)); methods for treating lung cancer in a patient, for example, by administering a treatment regimen that comprises a PD-1 axis binding antagonist (e.g., atezolizumab) to the patient. Also provided are compositions for use, kits, and articles of manufacture for use in classifying and treating lung cancer in a patient.

The present invention relates to therapeutic treatment of cancer, particularly mesothelioma, using Compound IA as single agent or in combination therapy using Compound IA and atezolizumab.

The invention belongs to the technical field of biological medicine and immunology, and particularly relates to a single-domain antibody targeting PD-L1 cross binding of human and cynomolgus monkeys and application of the single-domain antibody. The single-domain antibody disclosed by the invention has the specificity of resisting PD-L1 of human and cynomolgus monkeys, and shows relatively strong binding efficacy in the binding detection of PD-L1 target protein or PD-L1 overexpression cells; in the detection of blocking PD-1 / PD-L1 functions, a part of the single-domain antibodies even show a blocking effect which is obviously superior to that of Atezolizumab, so that the single-domain antibodies prepared by the invention can be used for diagnosis, treatment and prognosis detection of PD-L1 positive tumors. Meanwhile, the single-domain antibody disclosed by the invention has cross-species cross binding capacity, can be directly used for preclinical pharmacodynamics and safety evaluation, does not need to develop a species-specific substitution antibody, and realizes'one target and double effects'.

A method for improving the survival of a subject with cancer is disclosed, comprising applying an alternating electric field having a predetermined frequency and electric field intensity to a target site of the subject containing one or more cancer cells for a predetermined period of time, and administering the subject a therapeutically effective amount of a checkpoint inhibitor. A method for treating a subject with cancer is disclosed, comprising applying an alternating electric field having a predetermined frequency and electric field intensity to a target site of the subject containing one or more cancer cells for a predetermined period of time, and administering the subject a therapeutically effective amount of a checkpoint inhibitor. In some embodiments, the checkpoint inhibitor is nivolumab, pembrolizumab, or atezolizumab. Furthermore, a method for improving the survival of a subject with non-small cell lung cancer is disclosed, comprising applying an alternating electric field having a predetermined frequency and electric field intensity to a target site of the subject containing one or more non-small cell lung cancer cells for a predetermined period of time, and administering the subject a therapeutically effective amount of a checkpoint inhibitor. A method for treating a subject having non-small cell lung cancer is disclosed, the method comprising applying an alternating electric field having a predetermined frequency and electric field intensity to a target site of the subject containing one or more non-small cell lung cancer cells for a predetermined period of time, and administering to the subject a therapeutically effective amount of a checkpoint inhibitor. In some embodiments, the checkpoint inhibitor is ipilimumab (Yervoy), pembrolizumab (Keytruda), nivolumab (Opdivo), semiprimab (brand name Ributayo), dostallimab (Jemperli), atezolizumab (Tecentriq), durvalumab (Imfinzi), or avelumab (Bavencio).

The invention belongs to the field of medicinal chemistry and pharmacology, and relates to application of a novel glycolipid TLR2 agonist 13-C in preparation of vaccine adjuvants and anti-tumor treatment. The compound is excellent in human TLR2 agonist activity, EC50 reaches 2.2 nM, and the compound is simple in structure, easy to prepare and excellent in solubility and has industrial application potential. In a B16-OVA tumor model, the antibody induction capacity of the compound is superior to that of a positive control drug Diprovocim, and the anti-tumor activity of the compound is more remarkable; in addition, PD-L1 expression of tumor tissue can be effectively down-regulated, and a synergistic anti-tumor effect is generated with a PD-L1 monoclonal antibody Atezolizumab. Besides, 13-C and a vaccine adjuvant QS-21 are combined for use, so that a synergistic enhancement effect is achieved, the antibody titer induced by a vaccine can be remarkably improved, antibody subtypes are enriched, meanwhile, cellular immunity and humoral immunity response of an organism are stimulated, and the effect of dual immune activation is achieved.

The present invention provides a bifunctional fusion protein of an anti-PD-1 antibody and an IL-2 mutant. The bifunctional fusion protein of the present invention comprises a PD-1 antibody and an IL-2 mutant connected by a mutated FC. The bifunctional fusion protein of the present invention has the functions of activating and amplifying PD-1 positive lymphocytes and regulating the activity of Treg cells, and can activate tumor immunity to treat cancer. The present invention also provides the application of the bifunctional fusion protein in the field of tumor treatment. The present invention also provides a combination therapy for treating tumors by combining the bifunctional fusion protein with atezolizumab.

Liquid pharmaceutical formulations comprising anti-PD-L1 antibodies for subcutaneous administration are provided.SOLUTION: Provided is a liquid pharmaceutical formulation comprising atezolizumab in a concentration of 100g / L to 150g / L, histidine-acetate in a concentration of 15mM to 25mM, sucrose in a concentration of 200mM to 280mM, polysorbate in a concentration of 0.04% (w / v) to 0.08% (w / v), methionine in a concentration of 5mM to 15mM, hyaluronidase in a concentration of 1000U / ml to / ml, and a pH of 5.6 to 6.0, wherein the liquid pharmaceutical formulation is for subcutaneous administration. 3000U.SELECTED DRAWING: Figure 9B

The present application relates to pyrazole derivatives as inhibitors of the PD-1 / PD-L1 interaction. The applicants have designed compounds of general formula (I) wherein R ', R2, y3, R3, R4, R5, R6 and R7 are as defined herein, which are effective in blocking PD-1 / PD-L1 interactions to restore an anti-tumor immune response in a subject and eradicate any tumors in which dormant tumor cells and PD-L1 participate in immune escape. The inventor verifies that these compounds block the PD-1 / PD-L1 interaction by performing physical and chemical tests (MST, NanoDSF) and in vitro biological tests (FRET assay, Pralomig block assay, T cell assay). These compounds have affinity (Kd) in the order of pM, which Kd is higher than the Kd of the antibody Atezumab used in clinical use, and have IC50 comparable to or higher than that observed using Atezumab. Therefore, the invention also relates to a pharmaceutical composition containing the compound and application of the pharmaceutical composition in treatment of PD-1-PD-L1 interaction related diseases (cancers, chronic inflammatory diseases, neurological diseases and chronic infections).

The present application belongs to the technical field of biological medicine and immunology, and particularly relates to a single-domain antibody targeting human and cynomolgus monkey PD-L1 cross-binding and application thereof. The single-domain antibody has specificity against human and cynomolgus monkey PD-L1, and shows strong binding efficiency in the binding detection with a PD-L1 target protein or a PD-L1 overexpression cell. In the detection of blocking PD-1 / PD-L1 function, part of the single-domain antibodies even show a blocking effect significantly better than Atezolizumab, which confirms that the single-domain antibody prepared by the present application can be used for the diagnosis, treatment and prognosis detection of PD-L1 positive tumors. Meanwhile, the single-domain antibody has cross-binding ability across species, and can be directly used for preclinical pharmacodynamics and safety evaluation, without the need to develop species-specific alternative antibodies, so as to achieve "one target with double effect".

Circulating tumor DNA (ctDNA) is a promising non-invasive biomarker in cancer. The inventors aim to assess the dynamic evolution of ctDNA in patients with hepatocellular carcinoma (HCC). For that, they analyzed 772 plasmas from 173 patients with HCC collected at the time of diagnosis or treatment (n=502), 24h after locoregional treatment (n=154), and during follow-up (n=116). All samples were analyzed for cell free DNA (cfDNA) concentration, and for mutations in TERT promoter, CTNNB1, TP53, PIK3CA and NFE2L2 by sequencing and droplet-based digital PCR. Results were compared to 232 corresponding tumor samples. In active HCC, the inventors identified 27-5% of mutations in TERT promoter, 21 -3% in TP53, 13- 1% in CTNNB1, 0-4% in PIK3CA and 0-2% in NFE2L2, most of the times similar to those identified in the corresponding tumor. In 103 patients treated by percutaneous ablation, the presence and number of mutations in the ctDNA before treatment were associated with higher risk of death (p=0 001 ) and recurrence (p<0 001). In patients treated by atezolizumab / bevacizumab, persistence of mutation in ctDNA was associated with radiological progression (63-6% versus 36-4% for disappearance, p=0 019). Thus, circulating tumor DNA offers dynamic information reflecting tumor biology and represents a non-invasive tool useful to guide HCC clinical management.

Kits for combination therapy are provided.SOLUTION: Provided is a kit for combination therapy comprising an anti-IL-2 antibody or a pharmaceutical composition comprising the same, IL-2 or a pharmaceutical composition comprising the same, and an immune checkpoint inhibitor or a pharmaceutical composition comprising the same. The immune checkpoint inhibitor is a programmed cell death ligand 1 (PDL-1) checkpoint inhibitor, or a programmed cell death protein 1 (PD-1), optionally, the PDL-1 checkpoint inhibitor is selected from avelumab, atezolizumab, durvalumab, segmariumab, and enbufolimab, and the PD-1 checkpoint inhibitor is selected from nivolumab, pembrolizumab, cemiplimab, camrelizumab, zingeberilumab, tislelizumab, sintilimab, teriplizumab, prologolimab, penprimumab and the like.SELECTED DRAWING: Figure 1

Provided is a bifunctional fusion protein comprising an anti-PD-1 antibody and an IL-2 mutant. The bifunctional fusion protein comprises the PD-1 antibody and the IL-2 mutant which are connected by a mutated FC. The bifunctional fusion protein has the effects of activating and amplifying PD-1 positive lymphocytes and regulating the activity of Treg cells, and can activate tumor immunity so as to treat cancers. Also provided is a use of the bifunctional fusion protein in the field of tumor treatment. Also provided is a combination therapy for treating tumors by combining the bifunctional fusion protein and atezolizumab.

Provided herein are combination therapies comprising a SHP2 inhibitor (e.g., Compound 1) and a PD-L1 binding antagonist (e.g., atezolizumab) and methods of using such combination therapies.

The invention provides methods and compositions for treating bladder cancer (e.g., urothelial carcinoma (UC), including locally advanced or metastatic UC) in a subject, for example, by administering a treatment regimen that includes a PD-1 axis binding antagonist (e.g., atezolizumab) to the patient. Also provided are compositions (e.g., a PD-1 axis binding antagonist (e.g., atezolizumab) and / or a platinum-based chemotherapy (e.g., cisplatin or carboplatin and gemcitabine), pharmaceutical compositions thereof, kits thereof, and articles of manufacture thereof) for use in treating bladder cancer (e.g., UC, including locally advanced or metastatic UC) in a patient. Also provided are assays and methods for determining the presence and / or expression level of PD-L1 in a sample obtained from a patient and for labeling PD-L1 in a sample obtained from a patient.

The application discloses application of BRD7, all-trans retinoic acid and PD-L1 antibody in preparation of a preparation for treating nasopharyngeal carcinoma. In previous research, it is found that overexpression of BRD7 can inhibit expression of PD-L1 and inhibit proliferation of nasopharyngeal carcinoma cells; all-trans retinoic acid (ATRA) can significantly inhibit proliferation of the nasopharyngeal carcinoma cells and induce cell cycle arrest of the nasopharyngeal carcinoma cells; and the PD-L1 antibody (Atezolizumab) can block the interaction between the immune suppression checkpoints PD-1 / PD-L1, so that T cells are reactivated and the killing effect on the nasopharyngeal carcinoma cells is enhanced. The combination of overexpression of BRD7, all-trans retinoic acid and the PD-L1 antibody brings good news to patients with nasopharyngeal carcinoma.

The present invention relates to therapeutic treatment of cancer, particularly mesothelioma, using ecubectedin (PM14) as single agent or in combination therapy using ecubectedin and atezolizumab.

The present invention relates to the treatment of cell proliferative disorders. More specifically, the invention relates to the specific treatment of human subjects having a solid tumor malignancy using anti-C-C motif chemokine receptor 8 (CCR8) / anti-cluster of differentiation 3 (CD3) bispecific antibodies alone or in combination with an anti-programmed death-ligand 1 (PD-L1) antibody (e.g., atezolizumab).

The invention provides methods for classifying bladder cancer (e.g., urothelial cancer (UC), e.g., locally advanced or metastatic UC); methods for treating bladder cancer in a patient, for example, by administering a treatment regimen that comprises a PD-1 axis binding antagonist (e.g., atezolizumab) to the patient. Also provided are compositions for use, kits, and articles of manufacture for use in classifying and treating bladder cancer in a patient.

The present disclosure relates to methods, uses, and kits related to treating cancers by administering an anti-PD-L1 antibody (e.g., atezolizumab) to a patient. In some embodiments, the anti-PD-L1 antibody is administered in 840 mg every 2 weeks or 1680 mg every 4 weeks for two or more cycles.