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Comment
. 2015 Dec;5(12):1238-40.
doi: 10.1158/2159-8290.CD-15-1275.

Overcoming Antigen Escape with CAR T-cell Therapy

Hollie J Jackson  1 , Renier J Brentjens  2
Affiliations
Comment

Overcoming Antigen Escape with CAR T-cell Therapy

Hollie J Jackson et al. Cancer Discov. 2015 Dec.

Abstract

Sotillo and colleagues describe the molecular events associated with apparent loss of target antigen expression following CAR T-cell therapy. We propose that broader immune activation is required to prevent outgrowth of tumor antigen escape variants following targeted therapies.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest

R.J. Brentjens is a scientific co-founder of, reports receiving a commercial research grant from, has ownership interest (including patents) in, and is a consultant/advisory board member for JUNO Therapeutics. No potential conflicts of interest were disclosed by the other author.

Figures

Figure 1
Figure 1
Immune modulation is required to eradicate tumors in the context of CAR T-cell therapy. A, Sotillo and colleagues (5) describe the molecular mechanisms associated with outgrowth of tumor cells that have mutated the CAR target TAA, resulting in relapse of antigen-negative tumor following CAR T-cell therapy. B, we hypothesize that CAR T-cell therapy with recruitment of endogenous antitumor immune cells will allow epitope spreading and complete eradication of tumor cells even when tumor cells have mutated the CAR target TAA.
See this image and copyright information in PMC

Comment on

  • Convergence of Acquired Mutations and Alternative Splicing of CD19 Enables Resistance to CART-19 Immunotherapy.
    Sotillo E, Barrett DM, Black KL, Bagashev A, Oldridge D, Wu G, Sussman R, Lanauze C, Ruella M, Gazzara MR, Martinez NM, Harrington CT, Chung EY, Perazzelli J, Hofmann TJ, Maude SL, Raman P, Barrera A, Gill S, Lacey SF, Melenhorst JJ, Allman D, Jacoby E, Fry T, Mackall C, Barash Y, Lynch KW, Maris JM, Grupp SA, Thomas-Tikhonenko A. Sotillo E, et al. Cancer Discov. 2015 Dec;5(12):1282-95. doi: 10.1158/2159-8290.CD-15-1020. Epub 2015 Oct 29. Cancer Discov. 2015. PMID: 26516065 Free PMC article.

References

    1. Pegram HJ, Smith EL, Rafiq S, Brentjens RJ. CAR therapy for hematological cancers: can success seen in the treatment of B-cell acute lymphoblastic leukemia be applied to other hematological malignancies? Immunotherapy. 2015;7:545–61. - PMC - PubMed
    1. Grupp SA, Maude SL, Shaw P, Aplenc R, Barrett DM, Callahan C, et al. T cells engineered with a chimeric antigen receptor (CAR) targeting CD19 (CTL019) have long term persistence and induce durable remissions in children with relapsed, refractory ALL. Blood. 2014;124:380.
    1. Park JH, Riviere I, Wang X, Bernal Y, Purdon T, Halton E, et al. Efficacy and safety of CD19-targeted 19–28z CAR modified T cells in adult patients with relapsed or refractory B-ALL. J Clin Oncol. 2015;33(suppl) abstr 7010.
    1. Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385:517–28. - PMC - PubMed
    1. Sotillo E, Barrett DM, Black KL, Bagashev A, Oldridge D, Wu G, et al. Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov. 2015;5:1282–95. - PMC - PubMed

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