Provided are a human PD-1 antibody, an antigen-binding fragment thereof and a medical use thereof. A chimeric antibody containing a complementarity determining region (CDR) of the antibody, a pharmaceutical composition containing the human PD-1 antibody and the antigen-binding fragment thereof, and a use of the antibody in preparation of a drug for treating a disease or a disorder are further disclosed.

Provided are anti-TIGIT antibodies that bind to “T cell immunoreceptor with Ig and ITIM domains (TIGIT)”, including multispecific anti-TIGIT antibodies with binding specificity for TIGIT and one or more additional antigen, and methods of using the same. In certain embodiments, the anti-TIGIT antibodies comprises a single domain antibody that binds to TIGIT. In certain embodiments, the one or more additional antigen comprises Programmed cell death ligand 1 (PDL1).

This disclosure relates to modified immunoglobulins.

A multispecific nanobodies chimeric antigen receptor and T-cell engager includes an HLA-G nanobody chimeric antigen receptor and a bispecific T-cell engager. The HLA-G nanobody chimeric antigen receptor includes an HLA-G nanobodies unit, a transmembrane domain, and a CD3z signaling domain. The bispecific T-cell engager includes a PD-L1 nanobodies unit and a CD3e nanobody.

Use of a CXCR4 antagonistic peptide and an immune-check point regulator in the treatment of cancer is provided. Accordingly there is provided a method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a peptide having an amino acid sequence as set forth in SEQ ID NO: 1 or an analog or derivative thereof; and a therapeutically effective amount of a PD1 antagonist, a PDL-1 antagonist, a CTLA-4 antagonist, a LAG-3 antagonist, a TIM-3 antagonist, a KIR antagonist, an IDO antagonist, an OX40 agonist, a CD137 agonist, a CD27 agonist, a CD40 agonist, a GITR agonist, a CD28 agonist or an ICOS agonist, thereby treating the cancer in the subject. Also provided are pharmaceutical compositions and articles of manufacture.

Provided are a bifunctional fusion protein and pharmaceutical use thereof. Specifically, provided are a bifunctional fusion protein comprising an SIRPγ peptide variant and an anti-human PD-L1 antibody, an SIRPγ peptide variant, and pharmaceutical use thereof. The bifunctional fusion protein can specifically bind PD-L1 and CD47 to block the binding of PD-L1 or CD47 to a receptor or ligand thereof. In addition, also provided are preparation and application of the bifunctional fusion protein, and treatment of cancers and immune-related diseases.

The invention pertains to antibodies or other antigen binding proteins targeting the CD276 antigen, also known as B7-H3. The invention provides an improved set of antibodies which bind at new positions within the CD276 antigen and are of particular use as therapeutics in the treatment of CD276 positive cancer. Further the invention provides antibody conjugate and bispecific antibodies which were developed on basis of the novel anti-CD276 antibodies of the invention. Furthermore, the invention discloses the therapeutic use of the antibodies and other modulators in the treatment of CD276 positive cancer. Finally, the nucleic acid constructs encoding the molecules of the invention, recombinant cells expressing them, as well as particular uses and methods are provided.

A cold atmospheric plasma (CAP)-mediated ICB therapy/delivery device are disclosed herein that employs a patch having microneedles that are used to deliver the CAP transdermally along with an immune checkpoint inhibitor for enhancing transdermal treatment efficacy. The hollow-structured microneedle patch can facilitate the transportation of CAP through the skin, causing tumor cell death. The release of cancer antigens then promotes the maturation of dendritic cells in the tumor-draining lymph nodes, subsequently initiating the T cell-mediated immune response. Anti-PDL1 antibody (aPDL1), an immune checkpoint inhibitor (or other immune checkpoint inhibitors), released from the microneedle patch (in some embodiments) further augments the anti-tumor immunity. The transdermal combinational CAP and ICB therapy inhibits tumor growth for both primary tumors as well as distant tumors, with prolonged survival in the tumor-bearing mice. Such results should translate to other species.

The present invention relates to an immunocytokine comprising an heterodimeric protein complex based on IL-15/IL-15Rα, and to use thereof as a therapeutic agent, in particular as an agent for the treatment of cancer and an autoimmune disease. The present invention further relates to an immunocytokine comprising a heterodimeric protein complex based on an IL-15/IL-15Rα and an immunomodulatory antibody, and to use thereof as a therapeutic agent, in particular as an agent for the treatment of cancer and an autoimmune disease.

The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a multi-RTK inhibitor, and the use of the combination therapies for the treatment of cancer. The multi-RTK inhibitor may be represented by Formula (I): ##STR00001## wherein R.sup.1 is C.sub.1-6 alkyl or C.sub.3-8 cycloalkyl, R.sup.2 is a hydrogen atom or C.sub.1-6 alkoxy, and R.sup.3 is a hydrogen atom or a halogen atom. A tumor therapeutic agent is disclosed that combines a compound or pharmaceutically acceptable salt thereof represented by Formula I and an anti-PD-1 antibody.