19 results about "Immunotoxin" patented technology

The invention discloses a novel application of a small molecule compound BRD4780 in resisting ricin, the small molecule compound BRD4780 has a remarkable effect of resisting ricin toxicity and can be used in development of anti-ricin drugs, a brand new candidate molecule is provided for development of the anti-ricin drugs, the drug research and development blank in the field is filled, and the application of the small molecule compound BRD4780 in resisting ricin is developed. The method has important significance in the aspects of clinical treatment, biological protection and immunotoxin treatment safety optimization, and is wide in application prospect.

The present invention discloses a novel application of the small molecule compound BRD4780 in anti-ricin toxin treatment. The small molecule compound BRD4780 has a significant anti-ricin toxin toxicity effect and can be used in the development of anti-ricin drugs. The present invention provides a new candidate molecule for the development of anti-ricin drugs, filling the gap in drug research and development in this field. It is of great significance in clinical treatment, biological protection and optimization of immunotoxin treatment safety, and has broad application prospects.

It is an object of the present invention to provide a compound that has absorption in a near infrared region, has high efficiency of singlet oxygen generation (quantum yield), and also has high tumor toxicity when it is combined with an immunotoxin. According to the present invention, provided is a compound represented by the following formula (1) or a salt thereof:wherein L1 and L2 each independently represent a single bond, —O—, —CO—, an alkylene group containing 1 to 8 carbon atoms, a sugar chain, or a combination thereof; R1 and R2 each independently represent an alkyl group containing 1 to 8 carbon atoms, a carboxylic acid group, an amino group, a hydroxyl group, a thiol group, or a biotin residue; R3, R4, R5, R6, R7 and R8 each independently represent an alkyl group containing 1 to 8 carbon atoms, a phenyl group, a carboxylic acid group, an amino group, a hydroxyl group, a thiol group, or a biotin residue; and M represents Mg, Zn, Fe, P, Si, Cu, Sn, Al, Ti, Mo, or Ni.

The invention discloses an antibody for specifically targeting IL-4R (interleukin-4R) and an immunotoxin of the antibody. The antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3. The invention also discloses an immunotoxin containing the antibody, a nucleic acid encoding the antibody, a recombinant expression vector and a transformant containing the antibody, a pharmaceutical composition containing the antibody, a kit and a kit kit. The invention also discloses an application of the antibody in preparation of drugs for diagnosis and / or treatment of IL-4R positive tumors. The antibody provided by the invention can be combined with IL-4R in a high affinity manner, and the effect of the antibody is equivalent to that of Dupilumab; the immunotoxin provided by the invention has a relatively strong killing effect on breast cancer cells, and the IC50 value of the immunotoxin is less than 10nM.

Monoclonal antibodies that bind glypican-2 (GPC2) with high affinity are described. Immunotoxins and chimeric antigen receptors (CARs) that include the disclosed antibodies or antigen-binding fragments thereof are further described. In some instances, the antibody or antigen-binding fragment is humanized. The disclosed GPC2-specific antibodies and conjugates can be used, for example, for the diagnosis or treatment of GPC2-positive cancers, including neuroblastoma, medulloblastoma and retinoblastoma.

Methods of treating patients suffering from cancer using a combination of 1) an immunomodulatory agent; 2) a check point inhibitor; and 3) a cancer antigen releasing therapy are provided. In some aspects, the immunomodulatory agent is an anti-CD3 immunotoxin, the check point inhibitor inhibits the interaction of PD-1 and PD-L1 and the cancer antigen releasing therapy is radiation.

This invention relates to an immunotoxin targeting hematologic malignancies and its application. The immunotoxin comprises a toxic molecule and a carrier. The toxic molecule is pumpkin protein or a mutant of pumpkin protein. The carrier contains an antibody, ligand, or polypeptide capable of binding to hematologic malignancies cells. The antibody comprises an antibody fragment or a small molecule antibody. This invention provides an immunotoxin targeting hematologic malignancies for the treatment of these malignancies. The immunotoxin using a pumpkin protein mutant as the toxic molecule exhibits enhanced specificity against hematologic malignancies cells with high target expression, significantly increased activity in killing target cells, and allows for a substantial reduction in dosage and toxicity. In summary, the immunotoxin targeting hematologic malignancies using a pumpkin protein mutant as the toxic molecule offers advantages in both synergistic effect and reduced toxicity, and has broad application prospects.

This disclosure relates to immunotoxin fusion proteins that comprise a bivalent single-chain fragment variable that specifically binds to the thrombopoietin receptor (cMPL); and a diphtheria toxin. The disclosure also provides compositions comprising such proteins and nucleic acid molecules encoding such proteins and uses thereof.

The present invention provides a plurality of monoclonal antibodies capable of recognizing glypican 3 (GPC3) with high affinity. The monoclonal antibodies not only have high affinity, but also cover a plurality of epitopes of GPC3, and can be used for detecting a tumor marker GPC3 by a sandwich method. The monoclonal antibody provided by the invention not only has good thermal stability, but also has excellent cytotoxic activity after being conjugated with pseudomonas exotoxin PE24, is obviously superior to the existing immunotoxin HN3-PE24, and can be used for developing immunotoxin or antibody-drug conjugate (ADC) drugs with stronger activity and better stability.

Provided herein are engineered effector cells that include a toxin expressing module, wherein the toxin expressing module expresses a toxin, and wherein the engineered effector cell is resistant to the toxin. In some embodiments, the engineered effector cell further includes a chimeric antigen receptor (CAR), wherein the CAR binds specifically to a tumor antigen.

The present invention provides a composition comprising a first antibody molecule that specifically recognizes CD3 and a second antibody molecule that specifically recognizes CD7, for use in a method of treatment, or preventative treatment of viral infection or viral reactivation in a mammalian subject undergoing immunomodulatory treatment, wherein the first and second antibody molecules are each provided with a toxic moiety. Also provided is a method of treating a mammalian subject having, or being at risk of developing, chronic Graft versus Host disease (cGVHD). Also provided is a related pharmaceutical composition.

Disclosed herein are methods of preventing and treating acute GVHD and chronic GVHD after hematopoietic cell transplantation (HCT), as well as methods of in vivo augmenting expansion of donor CD8+ T cells in the lymphoid tissues in vivo after HCT and methods of augmenting recipient tissue expression of programmed death-ligand 1 (PD-L1, or B7H1) after HCT. The methods entail administering one or more doses of an effective amount of a therapeutic agent to a recipient simultaneously, immediately before, or immediately after HCT to temporarily deplete CD4+ T cells or to reduce serum IL-2. Some examples include an anti-CD4 antibody or an anti-CD4-meditope-immunotoxin, an anti-IL-2 antibody, an agent blocking IL-2R, and / or a PD-L1-Ig. One or more additional therapeutic agents such as IFN-γ can be administered.

IL2-CCR4 bispecific immunotoxin, CCR4-IL2 bispecific immunotoxin, and methods of use thereof for treatment of refractory and recurrent human CD25.sup.+ and / or CCR4.sup.+ cutaneous T cell lymphoma, and other human CD25.sup.+ or CCR4.sup.+ tumors. The bispecific immunotoxin can be also used for broad cancer treatment via depleting CD25.sup.+ or CCR4.sup.+ Tregs.

Human anti-CD45 antibodies are described. The anti-CD45 antibodies can be engineered into numerous formats, such as antibody-radioisotope conjugates, antibody-immunotoxin conjugates, antibody-drug conjugates (ADCs), antibody-detectable label conjugates, antibody-nanoparticle conjugates, antibody-bead conjugates, multi-domain binding molecules, single chain variable fragments (scFv), and recombinant receptors and can be used as research, diagnostic, or therapeutic tools against CD45-related disorders. Examples of CD45 related disorders include cancers (solid tumors and hematologic malignancies such as acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)), infections, autoimmune disorders, and metabolic disorders, among other disorders described herein.

IL2-CCR4 bispecific immunotoxin, CCR4-IL2 bispecific immunotoxin, and methods of use thereof for treatment of refractory and recurrent human CD25+ and / or CCR4+ cutaneous T cell lymphoma, and other human CD25+ or CCR4+ tumors. The bispecific immunotoxin can be also used for broad cancer treatment via depleting CD25+ or CCR4+ Tregs.

The invention discloses a shark single-domain antibody 4A1 targeting FAP and an application of the shark single-domain antibody 4A1. The amino acid sequence of the shark single-domain antibody 4A1 is as shown in SEQ ID No. 1, and the nucleotide sequence of the encoding gene of the shark single-domain antibody 4A1 is as shown in SEQ ID No. 2. The molecular weight of the shark single-domain antibody 4A1 prepared by the invention is about 15 kDa and is smaller than that of a traditional monoclonal antibody, the stability is high, the tissue permeability is good, and the 4A1 can be expressed by utilizing an escherichia coli prokaryotic expression system. The antibody can be used for constructing immunotoxin fusion protein, the immunotoxin has good killing activity on FAP-positive tumor cells or cancer-related fibroblasts, subsequent effective treatment can be carried out on tumors independently or in combination with other anti-tumor drugs, and a new thought is provided for tumor treatment and antibody drug research and development.

Methods of treating various types of cancer, including breast cancer, involve administering a therapeutically effective amount of a pharmaceutical composition containing a genetically engineered C-C Motif Chemokine Receptor 4 immunotoxin alone or in combination with one or more additional therapeutic agents, such as a pharmaceutical composition containing an anti-programmed death-1 monoclonal antibody.

Methods of treating various types of cancer, including cutaneous T-cell lymphoma, involve administering a therapeutically effective amount of a pharmaceutical composition containing a genetically engineered C-C motif chemokine receptor 4 bispecific immunotoxin, alone, or in combination with one or more additional therapeutic agents, such as a pharmaceutical composition containing an antibody-drug conjugate.

The invention discloses a shark single-domain antibody targeting to TROP2 and an application of the shark single-domain antibody. The shark single-domain antibody targeting the TROP2 and the immunotoxin of the shark single-domain antibody are 4C6 with the amino acid sequence shown as SEQ ID NO.1. The invention further discloses a nucleotide sequence of the coding gene of the shark single-domain antibody and the immunotoxin of the shark single-domain antibody. The nucleotide sequence of the coding gene is shown as SEQ ID NO.2. The shark single-domain antibody prepared by the invention is small in molecular weight, high in stability and good in tissue permeability, has good affinity and specificity with TROP2, and has good selectivity for TROP2 positive tumor cells. The antibody can be used for constructing immunotoxin, an antibody-coupled drug (ADC), a nuclide-coupled drug (RDC), antibody fusion protein, CAR-T, CAR-NK cells and the like, and can also be used for developing in-vitro diagnostic reagents and scientific research reagents. The invention lays a foundation for tumor treatment and development of antibody drugs.