OX40 engagement depletes intratumoral Tregs via activating FcγRs, leading to antitumor efficacy.

Antibodies targeting checkpoint inhibitors or co-stimulatory receptors on T cells have shown significant antitumor efficacy in preclinical and clinical studies. In mouse tumor models, engagement of activating Fcγ receptor (FcγR)-expressing immune cells was recently shown to be required for the tumoricidal activity of antibodies recognizing the tumor necrosis factor superfamily receptor (TNFR) GITR (CD357) and CTLA-4 (CD152). In particular, activating FcγRs facilitated the selective elimination of intratumoral T-cell populations.

Activating Fc γ receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies.

Fc γ receptor (FcγR) coengagement can facilitate antibody-mediated receptor activation in target cells. In particular, agonistic antibodies that target tumor necrosis factor receptor (TNFR) family members have shown dependence on expression of the inhibitory FcγR, FcγRIIB. It remains unclear if engagement of FcγRIIB also extends to the activities of antibodies targeting immunoregulatory TNFRs expressed by T cells.

Biologic markers and breast cancer: a multiparametric study--1. Increased serum protein levels.

From early 1972 to the end of 1976, the profiles of several serum protein were used to monitor disease stage and prognosis of 207 patients with breast cancer. Six of these proteins, alpha 1-antitrypsin (alpha-AT), alpha 2-ceruloplasmin (Cp), beta 1-transferrin, IgA, C4, and C5, were significantly elevated in these cancer patients and were used as biologic markers in a multiparametric study. Among these breast cancer patients, 72% had at least two of these protein levels elevated, of which alpha-AT (55%), C5 (38%), and IgA (36%) levels were most commonly raised.

A clinical and immunological study of the effects of transfer factor on multiple sclerosis patients.

A clinical and laboratory trial was designated to test the value of a potentially active pool of transfer factor (TF) given for a period of 3 months, at weekly intervals, in 27 relapsing MS patients and controls. The pool of TF was extracted from peripheral lymphocytes of 36 normal individuals presensitized with DNCB as marker. It was biologically capable of transferring DNCB sensitivity to MS recipients and did not show any toxicity.

Immunological features in multiple sclerosis.

A clinical and laboratory profile of the immunological system of patients with multiple sclerosis (MS) strongly suggested that many specific immune deficiencies exist in MS. The immunological history showed that patients with MS had had more tonsillectomies, appendicectomies, and childhood infections than matched controls, which suggested that there had been problems in controlling various types of childhood infections. The cell-mediated immune response and the circulating antibody titres were specifically impaired against a variety of antigens.