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CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 antibodies of varying formulations have been evaluated in the clinic and found to be tolerable and feasible. Administration is associated with mild to moderate (but transient) cytokine release syndrome, readily managed in the outpatient setting. Antitumor activity with or without anti-CTLA4 monoclonal antibody (mAb) therapy has been observed in patients with melanoma, and major tumor regressions have been observed in patients with pancreatic cancer, mesothelioma, and other tumors in combination with chemotherapy. In a recent study of chemotherapy plus CD40 mAb, with or without PD-1 mAb, the objective response rate in patients with untreated, metastatic pancreatic cancer was >50%. Mechanistically, the combination of chemotherapy followed by CD40 mAb functions as an in situ vaccine; in addition, destruction of stroma by CD40-activated macrophages may enhance chemotherapy delivery. Evidence to date suggests that CD40 activation is a critical and nonredundant mechanism to convert so-called cold tumors to hot ones (with prominent tumor infiltration of T cells), sensitizing them to checkpoint inhibition. Expected final online publication date for the , Volume 71 is January 27, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
This article was published in the following journal.
Name: Annual review of medicine
Several recent studies have assessed suitability of tumor antigens for immunotherapy. Based on the restricted expression pattern in somatic tissues, cancer-testis antigens (CTAs) are possible candidat...
Programmed death-1 (PD-1) is a cell surface receptor that functions as a T cell checkpoint and plays a central role in regulating T cell exhaustion. Binding of PD-1 to its ligand, programmed death-lig...
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With the mechanistic understanding of immune checkpoints and success in checkpoint blockade using antibodies for the treatment of certain cancers, immunotherapy has become one of the hottest areas in ...
RATIONALE: Monoclonal antibodies, such as ticilimumab and CD40 agonist monoclonal antibody CP-870,893, can block tumor growth in different ways. Some block the ability of tumor cells to gr...
RATIONALE: Biological therapies such as flt3L and CD40-ligand use different ways to stimulate the immune system and stop cancer cells from growing. Biological therapy may be an effective t...
Systemic lupus erythematosus is an often devastating autoimmune disease which affects 1 in 2,000 women in the United States. Recently, several research laboratories have reported that a pr...
This phase I trial studies the side effects and best dose of TLR9 agonist SD-101 when given together with anti-OX40 antibody BMS 986178 and radiation therapy in treating patients with low-...
This study is for patients that have chronic lymphocytic leukemia (CLL). This research study aims to determine the safety and dosage of special cells that may make the patients own immune ...
A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.
A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Members of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. They are found on mature B-LYMPHOCYTES, some EPITHELIAL CELLS; and lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Form of adoptive transfer where cells with antitumor activity are transferred to the tumor-bearing host in order to mediate tumor regression. The lymphoid cells commonly used are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). This is usually considered a form of passive immunotherapy. (From DeVita, et al., Cancer, 1993, pp.305-7, 314)
Antibodies elicited in a different species from which the antigen originated. These antibodies are directed against a wide variety of interspecies-specific antigens, the best known of which are Forssman, Hanganutziu-Deicher (H-D), and Paul-Bunnell (P-B). Incidence of antibodies to these antigens--i.e., the phenomenon of heterophile antibody response--is useful in the serodiagnosis, pathogenesis, and prognosis of infection and latent infectious states as well as in cancer classification.
An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...
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