The invention relates to a method of determining an increased risk of cancer in an immunosuppressed patient, the method comprising: (a) determining the percentage of CD8+CD57+ T-cells in a population of CD8+ T-cells in a sample from the patient; wherein a percentage of 40% or greater of CD8+CD57+ T-cells is indicative of an increased risk of cancer; and/or (b) determining the percentage of CD4+CD57+ T-cells in a population of CD4+ T-cells in a sample from the patient; wherein a percentage of 10% or greater of CD4+CD57+ T-cells is indicative of an increased risk of cancer.

Antibodies and humanized variants thereof and their antigen-binding fragments and to other molecules that are capable of immunospecifically binding to the B7-H7 counter-receptor, H7CR, and their uses in enhancing immune responses and the treatment and diagnosis of cancer and other diseases are provided.

The present disclosure provides a method for treating a microsatellite stable cancer patient with a specific combination of medical agents or a composition or combination therefor. Specific combinations of medical agents include a combination of a cancer stem cell inhibitor (e.g., napabucasin) and an immune checkpoint inhibitor (e.g., pembrolizumab). The MSS patient can be selected by determining if the patient has one or more patient characteristics. Another aspect of the disclosure provides a method for predicting responsiveness of a patient to a cancer treatment based on one or more patient characteristics.

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.

The present invention relates to the field of tumor treatment and molecular immunology, and particularly, to an anti-PD-1 antibody and pharmaceutical use thereof. Specifically, the present invention relates to a monoclonal antibody, wherein a heavy chain variable region of the monoclonal antibody comprises CDRs with amino acid sequences of SEQ ID NOs: 19-21, and/or a light chain variable region of the monoclonal antibody comprises CDRs with amino acid sequences of SEQ ID NOs: 22-24; wherein according to the EU numbering system, a heavy chain constant region of the antibody comprises mutations at any 2 or 3 of positions 234, 235 and 237, and an affinity constant of the antibody to FcγRIIIa and/or C1q is reduced after the mutation as compared to that before the mutation. The monoclonal antibody of the present invention can be well and specifically bind to PD-1, specifically relieve immunosuppression of PD-1 in an organism 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.

The present disclosure relates generally to the analysis of immune checkpoint proteins involved in cancer. In particular, the present disclosure provides material and methods for determining abundance ratios of various immune checkpoint proteins (e.g., PD-1, PD-L1, and PD-L2) present in a biospecimen sample based on quantification of peak area using mass spectrometry analysis. The methods disclosed herein provide an alternative platform for diagnosing and treating cancer, especially in cases limited by ineffective antibody recognition.

The present invention provides De-ADCC/CDC activity monoclonal antibodies and their generation method and applications. The present invention modified the antibody sequences of multi-target sites such as PD-L1, PD-1, CTLA4, TNF-α, PCSK9, NGF, CD47 and C5. A flexible amino acid sequence was inserted between the heavy chain CDR3 and CH2 regions of IgG1 antibody to block the physical stress signal transmit from antigen-bound Fab to its Fc region to reduce the ADCC/CDC activity while not significantly increasing the formation of the polymers. The modified antibodies in the present invention and the original antibodies target the same sites, but the antibody subtype or glycosylation state is different. For the modified antibodies in the present invention, the stability is significantly improved or/and immunogenicity is significantly reduced, and the half-life is prolonged. The modified antibodies eliminate the activity of ADCC/CDC. Therefore, the antibody modified by the technology of the present invention can effectively avoid side effects caused by the activation of ADCC/CDC and other Fc-mediated functions and improve the curative effect of antibody drugs. It has excellent clinical application value and is suitable for promotion.

The present invention relates in a first aspect to a method for the stratification of a therapeutic regimen of a subject afflicted or suspected to be afflicted with an immune regulatory antibody-mediated disease based on the immune status of said subject, the method is based on determining the level or amount of expression of PD-1 in a predetermined subset of B-cells, thus, reflecting the immune tolerance status against an immune tolerance inducing compound of said subject. In addition, a method for monitoring of the development or progress of a treatment in a subject based on an administration of immune-tolerance-inducing compound containing antigenic epitopes recognized by the B-cells producing these antibodies. Further, a method for determining the risk of developing antibody-producing B-cells based failure of immune tolerance induction (ITI) treatment in a subject is provided. Moreover, the use of PD-1 expression as a marker in antibody-mediated disease based on B-cell tolerance status is described. Finally, a kit for use in determining antibody-producing B-cells for determining B-cell tolerance status in a predetermined set of B-cells is described.

The disclosure provides methods of determining patient populations amenable or suitable for immunomodulatory treatment of disease such as cancer by measuring the relative or absolute levels of T-cell sub-populations correlated with disease such as cancer.