Immunoglobulin Restores Immune Responses to BTH1677 in Patients With Low Levels of Antibodies to Beta-glucan

• Published in: Anticancer research Vol. 40; no. 3; pp. 1467 - 1473
• Main Authors: Hurley, Peter J, Bose, Nandita, Jha, Gautam, Gargano, Michele, Ottoson, Nadine, Gorden, Keith, Rathmann, Blaine, Harrison, Ben, Qiu, Xiaohong, Dudek, Arkadiusz Z
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.03.2020
• Subjects: Aged, 80 and over; Antibodies; Antibodies - blood; Antibodies - immunology; Antibodies, Monoclonal, Humanized - administration & dosage; Anticancer properties; Antineoplastic Agents, Immunological - administration & dosage; beta-Glucans - immunology; Cancer; Cetuximab - administration & dosage; Colorectal carcinoma; Colorectal Neoplasms - immunology; Colorectal Neoplasms - therapy; Disease control; Female; Glucan; Glucans - administration & dosage; Humans; Immune checkpoint inhibitors; Immune response; Immunoglobulins; Immunoglobulins - administration & dosage; Immunotherapy; Immunotherapy - methods; Intravenous administration; Levels; Metastases; Metastasis; Middle Aged; Monoclonal antibodies; Neuroendocrine tumors; Neuroendocrine Tumors - immunology; Neuroendocrine Tumors - therapy; Patients; Pembrolizumab; Targeted cancer therapy; β-Glucan; BTH1677; Imprime PGG; immunoglobulin; anti-beta glucan antibody; immunotherapy
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.14090

BTH1677 is a beta-glucan pathogen-associated molecular pattern (PAMP) being evaluated as a novel immunotherapy of cancer. We previously described that the presence of antibodies against beta-glucan (ABA) in serum is necessary for BTH1677 antitumoral activity. We hypothesized that infusion of immunoglobulin can reinstate responses to BTH1677 in individuals with low ABA levels. We report two single-patient studies: one in a patient with metastatic colorectal cancer who received BTH1677, combined with tumor targeting antibody cetuximab; and a second in a patient with metastatic neuroendocrine tumor who received BTH1677 combined with immune checkpoint inhibitor pembrolizumab. The patients had low serum titers of ABA and low innate immune effector functionality induced by BTH1677. Addition of intravenous immunoglobulins restored innate immune activity of BTH1677 and induced clinically meaningful anti-tumoral activity, with long-term disease control. Infusion of immunoglobulin can restore activity of BTH1677 in individuals with low serum ABA level.