Data from Determinants of Successful CD8<sup>+</sup> T-Cell Adoptive Immunotherapy for Large Established Tumors in Mice

Abstract

<div>Abstract<p><b>Purpose:</b> Adoptive cell transfer (ACT) of tumor infiltrating or genetically engineered T cells can cause durable responses in patients with metastatic cancer. Multiple clinically modifiable parameters can comprise this therapy, including cell dose and phenotype, <i>in vivo</i> antigen restimulation, and common gamma-chain (γ<sub>c</sub>) cytokine support. However, the relative contributions of each these individual components to the magnitude of the antitumor response have yet to be quantified.</p><p><b>Experimental Design:</b> To systematically and quantitatively appraise each of these variables, we employed the Pmel-1 mouse model treating large, established B16 melanoma tumors. In addition to cell dose and magnitude of <i>in vivo</i> antigen restimulation, we also evaluated the relative efficacy of central memory (T<sub>CM</sub>), effector memory (T<sub>EM</sub>), and stem cell memory (T<sub>SCM</sub>) subsets on the strength of tumor regression as well as the dose and type of clinically available γ<sub>c</sub> cytokines, including IL-2, IL-7, IL-15, and IL-21.</p><p><b>Results:</b> We found that cell dose, T-cell differentiation status, and viral vaccine titer each were correlated strongly and significantly with the magnitude of tumor regression. Surprisingly, although the total number of IL-2 doses was correlated with tumor regression, no significant benefit to prolonged (≥6 doses) administration was observed. Moreover, the specific type and dose of γ<sub>c</sub> cytokine only moderately correlated with response.</p><p><b>Conclusion:</b> Collectively, these findings elucidate some of the key determinants of successful ACT immunotherapy for the treatment of cancer in mice and further show that γ<sub>c</sub> cytokines offer a similar ability to effectively drive antitumor T-cell function <i>in vivo</i>. <i>Clin Cancer Res; 17(16); 5343–52. ©2011 AACR</i>.</p></div>