An anti-CTLA4 (cytotoxic T lymphocyte associated antigen 4) and anti-PD-1 (programmed cell death 1) bifunctional antibody. a pharmaceutical composition thereof and use thereof. Particularly, the anti-CLTA4 and anti-PD-1 bifunctional antibody comprises a first protein functional domain that targets PD-1 and a second protein functional domain that targets CTLA-4. The bifunctional antibody can bind to CTLA-4 and PD-1 specifically, relieve immunosuppression of CTLA4 and PD-1 on an organism specifically, activate T lymphocytes, and thus has good application prospects.

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.

Methods of determining suitability of a subject suffering from cancer or at risk of cancer relapse to receive treatment comprising an agent that reduces sCD28 levels are provided. Methods of treating a subject suffering from cancer or at risk of cancer relapse comprising administering an anti-PD-1/PD-L1 immunotherapy, measuring soluble CD28 levels in a subject, and administering an agent that reduces sCD28 levels to a subject whose sCD28 levels increased are also provided.

A polypeptide having a heavy chain variable region and/or light chain variable region that specifically binds to CTLA4 protein as well as antibodies and antibody fragments containing the heavy chain variable region and/or the light chain variable region that bind to CTLA4 protein. Pharmaceutical compositions and kits comprising the polypeptide or antibodies and antibody fragments containing the polypeptide are also provided.

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.

The present disclosure relates generally to methods and compositions for cancer immunotherapy, and more specifically, liquid markers for predicting effectiveness of cancer therapies. The disclosure features compositions and methods that are useful for predicting the efficacy of cancer treatment (e.g., a checkpoint inhibitor immunotherapy) and, in some embodiments, administering the cancer treatment such as immunotherapy.

Methods of diagnosing and predicting cancer relapse comprising measuring soluble CD28 levels in a subject, wherein an increase in soluble CD28 is indicative of cancer relapse or imminent cancer relapse, are provided. Methods of determining response to PD-1/PD-L1 based immunotherapy in a subject in need thereof, comprising measuring sCD28 levels in a subject undergoing PD-1/PD-L1 based immunotherapy at at least two time points wherein a decrease indicates response and an increase indicates lack of response, are also provided.

The present invention provides methods to improve a cancer patient's response to immune checkpoint inhibitor (ICI) therapy, and functional test to predict likelihood of response. Specifically, the invention provides methods to improve patient's response to immune checkpoint inhibitors using modulators and to predict response to the combination of immune checkpoint inhibitors and modulators.

The present invention belongs to the fields of tumor therapy and molecular immunology, and provides an anti-CTLA4 monoclonal antibody or antigen binding fragment thereof, a pharmaceutical composition thereof and use thereof. The monoclonal antibody of the present invention can block the binding of CLTA4 to B7, relieve the immunosuppression on the body by CTLA4, and activate T lymphocytes.

A polypeptide having a heavy chain variable region and/or light chain variable region that specifically binds to CTLA4 protein as well as antibodies and antibody fragments containing the heavy chain variable region and/or the light chain variable region that bind to CTLA4 protein. Pharmaceutical compositions and kits comprising the polypeptide or antibodies and antibody fragments containing the polypeptide are also provided.