Use of a Single CAR T Cell and Several Bispecific Adapters Facilitates Eradication of Multiple Antigenically Different Solid Tumors

• Published in: Cancer research (Chicago, Ill.) Vol. 79; no. 2; pp. 387 - 396
• Main Authors: Lee, Yong Gu, Marks, Isaac, Srinivasarao, Madduri, Kanduluru, Ananda Kumar, Mahalingam, Sakkarapalayam M, Liu, Xin, Chu, Haiyan, Low, Philip S
• Format: Journal Article
• Language: English
• Published: United States 15-01-2019
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-18-1834

: Most solid tumors are comprised of multiple clones that express orthogonal antigens, suggesting that novel strategies must be developed in order to adapt chimeric antigen receptor (CAR) T-cell therapies to treat heterogeneous solid tumors. Here, we utilized a cocktail of low-molecular-weight bispecific adapters, each comprised of fluorescein linked to a different tumor-specific ligand, to bridge between an antifluorescein CAR on the engineered T cell and a unique antigen on the cancer cell. This formation of an immunologic synapse between the CAR T cell and cancer cell enabled use of a single antifluorescein CAR T cell to eradicate a diversity of antigenically different solid tumors implanted concurrently in NSG mice. Based on these data, we suggest that a carefully designed cocktail of bispecific adapters in combination with antifluorescein CAR T cells can overcome tumor antigen escape mechanisms that lead to disease recurrence following many CAR T-cell therapies. SIGNIFICANCE: A cocktail of tumor-targeted bispecific adapters greatly augments CAR T-cell therapies against heterogeneous tumors, highlighting its potential for broader applicability against cancers where standard CAR T-cell therapy has failed.