Abnova Races Ahead to Develop and Commercialize Autologous T Cell Therapy for Solid Tumors

Neihu, Taiwan (March 8, 2018)

Abnova announced it has gained worldwide exclusive license of inducible tumor-infiltrating lymphocyte (iTIL) technology from MD Anderson Cancer Center, United States for the development and commercialization of autologous T cell therapy for solid tumors. Many immunotherapies have been employed to treat malignant tumors including monoclonal antibody, tumor vaccine, immune checkpoint blockade, tumor-infiltrating lymphocytes (TILs) and most recently chimeric antigen receptor (CAR) T cells. As tumors progress, all of these therapies fall short of immune cell penetration into tumors, tumor antigen escape, and immunosuppressive tumor microenvironment, resulting in relapsed and refractory disease which ends in the death of the patient. Overcoming these obstacles is the holy grail of immunotherapy, particularly for solid tumors. Addressing these unmet needs, Abnova has initiated the iTIL preclinical study by leveraging Takara Bio Japan’s contracted service for the production of GMP grade lentivirus for autologous T cell modification and cell processing. Abnova aims to complete the preclinical study by 2019 before entering into phase I human clinical trial.

The foundation of modern day cell therapy was laid by the pioneering work of Dr. Steven Rosenberg of National Institute of Health (NIH) using TIL therapy targeting refractory melanoma more than 20 years ago. Cell therapy gained a monumental success last year with the FDA’s approval of CAR T therapy against acute lymphoblastic leukemia (ALL) and diffuse large B cell lymphoma (DLBCL). Abnova’s iTIL technology is based on inducible infiltration of autologous T lymphocytes into solid tumors by a synergistic combination of low-dose chemotherapy plus a genetically engineered T cell which expresses membrane-bound form of interleukin 12 (IL-12) heterodimeric cytokine. IL-12 plays a pivotal role in the development of T cells and regulation of tumor microenvironment. The beneficial effects of IL-12 has long been recognized but systemic administration of IL-12 invariably results in significant toxicities thus preventing successful clinical applications. Nonetheless, the importance of IL-12 has led to the recent development of 4^th generation CAR T cells, so called TRUCK T cells which secret IL-12 to modulate the tumor microenvironment, but still failed to address the issues of T cell tumor penetration and tumor antigen escape. As a result, CAR T therapy has so far been ineffective against solid tumors and also suffers from cytokine release syndrome as a major side effect.

Dr. Shulin Li of MD Anderson Cancer Center who invented the iTIL technology has been mechanistically studied the role of IL-12 immunology and T cell therapy in the past two decades^{1, 2}. Dr. Li discovered that introducing membrane-bound IL-12 to T cells can facilitate deep penetration of T cells into solid tumors with promising therapeutic efficacy. This treatment not only boosted T cell infiltration into solid tumors, but also upregulated the levels of T cell-attracting chemokines, attracting T cells to the tumor microenvironment and enhancing the persistence of infiltrated T cells by improving the ratios of costimulatory and coinhibitory receptors. Application of iTIL technology has the potential to become the long-sought breakthrough in the treatment of solid tumors. It can also complement the already approved and the newly developing CAR T therapies by broadening their clinical applications in hematologic malignancies and negating the risk of cytokine release syndrome.

1. Hu J, Zhu S, Xia X, Zhang L, Kleinerman ES, Li S. CD8+ T cell-specific Induction of NKG2D Receptor by Doxorubicin plus Interleukin-12 and its Contribution to CD8+ T cell Accumulation in Tumors. Molecular Cancer 13(34): 1-13, 2014
2. Hu J, Bernatchez C, Zhang L, Xia X, Kleinerman ES, Huang MC, Hwu P, Li S. Induction of NKG2D Ligands on Solid Tumors required Tumor-Specific CD8+ T cells and Histone Acetyltransferases. Cancer Immunology Research 5(4): 300-311, 2017