The present invention relates to anti-PD-L1 binding members and in particular to monovalent, high potency PD-L1-binding antibody fragments being highly stable and soluble. Such binding members may be used in the treatment of cancer and inflammatory diseases as well as in diagnostics. Also provided are related nucleic acids, vectors, cells, and compositions.

Materials and methods for treating potentially chemoresistant tumors (e.g., using DNA-PKcs inhibitors and anti-B7-H1 antibodies) are provided herein.

In certain embodiments, the present invention provides a method of treating or preventing lupus (e.g., SLE) in a subject, comprising: (a) identifying the subject as having at least one differentially regulated biomarker selected from CD40, CD40L, CD86, CD80, and PD1; and (b) administering an agent that inhibits the CD40 or CD28 signaling pathway, thereby treating or preventing lupus in the subject. In other embodiments, the present invention provides a method of treating or preventing lupus (e.g., SLE) in a subject, comprising: (a) administering an agent that inhibits the CD40 or CD28 signaling pathway; (b) determining whether the agent neutralizes at least one differentially regulated biomarker selected from CD40, CD40L, CD86, CD80, and PD1; and (c) adjusting the dosing of the agent in the subject, thereby treating or preventing lupus in the subject.

Provided are an anti-VEGFA-anti-PD-1 bispecific antibody and a use thereof. Specifically, the anti-VEGFA-anti-PD-1 bispecific antibody comprises: a PD-1-targeted first protein functional region and a VEGFA-targeted second protein functional region. According to an EU numbering system, mutation occurs at two positions of positions 234 and 235 of a heavy chain constant region of the immunoglobulin contained in the bispecific antibody, and after the mutation, an affinity constant of the bispecific antibody with FcγRI, FcγRIIa, FcγRIIIa, and/or C1q is decreased compared to that before the mutation. The bispecific antibody can specifically bind to VEGFA and PD-1, specifically relieve immunosuppression of VEGFA and PD-1 on an organism, and inhibit tumor-induced angiogenesis, and thus has good application prospects.

Provided herein are agents, such as antibodies, antibody-drug conjugates, or chimeric antigen receptors, that target B7-H3. Methods of treating cancer are provided, comprising administering to a patient in need thereof an effective amount of an B7-H3-targeting agent. The patient may be selected for treatment if the cancer expresses an increased level of B7-H3.

The present invention provides therapeutic and diagnostic methods and compositions for cancer, for example, bladder cancer. The invention provides methods of treating bladder cancer, methods of determining whether a patient suffering from bladder cancer is likely to respond to treatment comprising a PD-L1 axis binding antagonist, methods of predicting responsiveness of a patient suffering from bladder cancer to treatment comprising a PD-L1 axis binding antagonist, and methods of selecting a therapy for a patient suffering from bladder cancer, based on expression levels of a biomarker of the invention (e.g., PD-L1 expression levels in tumor-infiltrating immune cells in a tumor sample obtained from the patient) and/or based on the determination of a tumor sample subtype.

A method for monitoring a patient's response to anti-Clever-1 therapy and estimating the need for combination therapy based on the expression levels of one or more cell surface marker selected from PD-1, PD-L1, CTLA-4, ICOS, OX40, 41BB, LAG3, TIM3, CD28, CD25 and CXCR3 on leucocytes in relation to anti-Clever-1 treatment and choosing the best combination agent to initiate treatment together with anti-Clever-1 therapy after observed changes in one or more cell surface marker expression.

Provided herein are B7-H3 antibodies, fragments of such antibodies, and compositions comprising the same. The antibodies, antibody fragments and compositions are useful in a number of analytical methods, including immunohistochemical and immunocytochemical detection and analysis of B7-H3. Also provided herein are isolated peptides and fusion proteins containing immunogenic determinants for said B7-H3 antibodies, animals immunized with the peptides and fusion proteins, isolated B cells obtained from the animals, and hybridomas made from the isolated B cells.

The present invention provides a novel use and methods comprising antibodies, or antigen-binding fragments thereof, which bind to a CCR7 receptor for use as a novel combination therapy with a BTK inhibitor and/or a Bcl-2 inhibitor in treatment of hyperproliferative blood malignancies, preferably in B-cell lymphomas, such as CLL. The combination can be used as first line, or in naïve patients not treated before with a BTK inhibitor and/or Bcl-2 inhibitor, or in patients with a BTK-inhibitor and/or Bcl-2-inhibitor refractory/relapsed disease. The antibodies and antigen-binding fragments are capable of selectively depleting ex vivo or in vitro malignant cells expressing CCR7 and are capable of impairing/blocking migration of said tumor cells towards CCR7 ligands. These effects are not related to previous or contemporary treatments with a BTK inhibitor and/or a Bcl-2 inhibitor. Similarly, the efficacy of the antibodies is not affected in patients that have relapsed/refractory disease. The use of said antibodies as a monotherapy or as a combination with a BTK inhibitor and/or a Bcl-2 inhibitor for depleting, killing and impairing/blocking migration and activation of tumor cells expressing CCR7 cells is disclosed, thus providing an alternative therapy treating hyperproliferative blood cancers.

Materials and methods for treating potentially chemoresistant tumors (e.g., using DNA-PKcs inhibitors and anti-B7-H1 antibodies) are provided herein.