53 results about "Anti ctla 4" patented technology

The present invention provides isolated monoclonal antibodies, particularly human monoclonal antibodies, that specifically bind to PD-1 with high affinity. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for detecting PD-1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-1 antibodies. The present invention further provides methods for using a combination immunotherapy, such as the combination of anti-CTLA-4 and anti-PD-1 antibodies, to treat hyperproliferative disease, such as cancer. The invention also provides methods for altering adverse events related to treatment with such antibodies individually.

The present invention provides methods for reducing the incidence of adverse events related to immunotherapy. More specifically, the present invention provides methods for reducing the incidence of enterocolitis associated with anti-CTLA-4 antibody immunotherapy.

The invention is directed to a method of predicting clinical response of a patient to treatment of a cancer by an immune checkpoint pathway inhibitor, such as an anti-CTLA-4 or anti-PD-1 antibody binding compound. In one aspect the method comprises generating pre- and post-treatment clonotype profiles, determining a number of clonotypes that decrease in frequency between the first and second clonotype profiles, and predicting a lack of responsiveness in the patient to the treatment whenever the number of clonotypes that decrease in frequency is greater than a predetermined value.

The present invention relates to the fields of life sciences and medicine. Specifically, the invention relates to cancer therapies. More specifically, the present invention relates to oncolytic adenoviral vectors and cells and pharmaceutical compositions comprising said vectors. The present invention also relates to said vectors for treating cancer in a subject and a method of treating cancer in a subject. Furthermore, the present invention relates to methods of producing monoclonal anti-CTLA4 antibodies in a cell and increasing tumor specific immune response and apoptosis in a subject, as well as uses of the oncolytic adenoviral vectors for producing monoclonal anti-CTLA4 antibodies in a cell and increasing tumor specific immune response and apoptosis in a subject.

The invention discloses a nanometer antibody Nb16 for anti-CTLA-4 and a preparation method and application of the nanometer antibody Nb16. The provided nanometer antibody comprises a determinant complementary region and a frame region. The determinant complementary region of the nanometer antibody includes CDR1, CDR2 and CDR3, wherein the amino acid sequence of CDR1 is the 26-35 amino acid of SEQ ID No.1 in a sequence list, the amino acid sequence of CDR2 is 51<st>-59 amino acid of SEQ ID No.1 in a sequence list, and the amino acid sequence of CDR3 is 97-106 amino acid of SEQ ID No.1 in a sequence list. The nanometer antibody Nb16 can combine with T cells and CTLA-4, and can be used for researching and developing a CTLA-4 molecular detection agent, preparing a tumor inhibitor or a tumor cell inhibitor, and preparing a medicine for inhibiting activity of CTLA-4 and prompting T cell proliferation.

Provided herein are methods of treating non-small cell lung cancers comprising administering an effective amount of MEDI4736 or an antigen-binding fragment thereof and tremelimumab or an antigen-binding fragment thereof.

The invention discloses an anti-CTLA-4 nano antibody Nb91 and a preparation method and an application thereof. The nano antibody provided by the invention includes a determinant complementary region and a frame region; the determinant complementary region of the nano antibody consists of CDR1, CDR2 and CDR3; an amino acid sequence of the CDR1 comprises 26th-32nd amino acids of SEQ ID NO.7 in a sequence table; an amino acid sequence of the CDR2 comprises 48th-55th amino acids of SEQ ID NO.7 in the sequence table; an amino acid sequence of the CDR3 comprises 94th-106th amino acids of SEQ ID NO.7 in the sequence table. The nano antibody Nb91 can be combined with T cells and CTLA-4, and can be applied to research and development of CTLA-4 molecular detection reagents, preparation of tumor inhibitors or tumor cell inhibitors and preparation of drugs for inhibition of CTLA-4 activity and promotion of T cell proliferation.

The invention provides a method of treating a melanoma comprising (i) identifying a patient having a PD-L1-negative melanoma and (ii) administering to the patient a combination of an anti-PD-1 antibody or an antigen-binding portion thereof and an anti-CTLA-4 antibody or an antigen-binding portion thereof. The methods of the invention can extend progression-free survival for over 8 months and/or reduces the tumor size at least about 10%, about 20%, about 30%, about 40%, or about 50% compared to the tumor size prior to the administration.

Provided herein are activatable anti-human CTLA-4 antibodies comprising a heavy chain comprising a VH domain and a light chain comprising a masking moiety (MM), a cleavable moiety (CM), and a VL domain. Such activatable anti-human CTLA-4 antibodies have CTLA-4 binding activity in the tumor microenvironment, where the masking moiety is removed by proteolytic cleavage of the cleavable moiety by tumor-specific proteases, but exhibit greatly reduced binding to CTLA-4 outside the tumor. In this way, the activatable anti-human CTLA-4 antibodies of the present invention retain anti-tumor activity while reducing the side effects associated with anti-CTLA-4 activity outside the tumor.

The present invention provides anti-CTLA-4 antibodies having enhanced ADCC activity, and their use in treating cancer. In one embodiment, the anti-CTLA-4 antibody is ipilimumab, and ADCC activity is enhanced by introducing G236A, S239D, A330L and I332E mutations (“GASDALIE”) into the Fc region of the heavy chain constant domain.

A method of treating cancer comprising and reducing autoimmune side effects in administration of anti-CTLA-4 antibodies. The invention provides methods for low dose immune checkpoint (IC) treatment of metastatic cancer by delivering anti-CTLA-4 and anti-PD-1 antibodies to cancer patients. Methods also provide for IL-2 stimulation for the activation of T cells against tumor cells. The invention further provides methods for daily cyclic high fever response (hyperthermia) during IL-2 therapy. The methods provide treatment of metastatic cancer without unacceptable autoimmune side effects.

The disclosure features a CXCR2 antagonist in combination with a checkpoint inhibitor (e.g., an anti-CTLA-4 antibody or an anti-PD-L1 antibody) and methods of using the combination to enhance anti-tumor activity in a subject.