Building upon the success of CART19: chimeric antigen receptor T cells for hematologic malignancies

Abstract

Chimeric antigen receptor T cell (CART) therapy has dramatically changed the therapeutic prospects for B cell malignancies. Over the last decade CD19-redirected CART have demonstrated the ability to induce deep, long-lasting remissions and possibly cure patients with relapsing B cell neoplasms. Such impressive results with CART19 fostered efforts to expand this technology to other incurable malignancies that naturally do not express CD19, such as acute myeloid leukemia (AML), Hodgkin lymphoma (HL) and multiple myeloma (MM). However, to reach this goal, several hurdles have to be overcome, in particular: (i) the apparent lack of suitable targets as effective as CD19; (ii) the immunosuppressive tumor microenvironment; (iii) intra-tumoral heterogeneity and antigen-negative relapses. Therefore, new strategies that allow safer and more potent CART platforms are under development and may provide grounds for new exciting breakthroughs in the field.

Keywords:

• CART19
• chimeric antigen receptor T cells
• hematologic malignancies
• Myeloid Leukemias and Dysplasias
• Lymphoma and Hodgkin disease
• Myeloma

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1403024.

Additional information

Funding

A. R. is supported by a Bloodwise Clinical Research Fellowship and A. K. is supported by a Bloodwise Program Grant [14009]. A. R. and A. K. acknowledge infrastructure support from the Cancer Research UK Imperial Centre, the Imperial Experimental Cancer Medicine Centre and the National Institute for Health Research Imperial Biomedical Research Centre. M. R. is supported by grants from the Univ. of Pennsylvania-Novartis Alliance, the NIH-NCI (K99 CA212302-01A1), the Gabrielle’s Angel Foundation, American Society of Hematology (Scholar Award), the Parker Institute for Cancer Immunotherapy and Tmunity therapeutics.