American Association for Cancer Research
10780432ccr141559-sup-132541_3_supp_2856592_njjz2z.pptx (901.36 kB)

Supplementary Figure S7 from Adoptive Transfer of MAGE-A4 T-cell Receptor Gene-Transduced Lymphocytes in Patients with Recurrent Esophageal Cancer

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posted on 2023-03-31, 18:31 authored by Shinichi Kageyama, Hiroaki Ikeda, Yoshihiro Miyahara, Naoko Imai, Mikiya Ishihara, Kanako Saito, Sahoko Sugino, Shugo Ueda, Takeshi Ishikawa, Satoshi Kokura, Hiroaki Naota, Kohshi Ohishi, Taizo Shiraishi, Naoki Inoue, Masashige Tanabe, Tomohide Kidokoro, Hirofumi Yoshioka, Daisuke Tomura, Ikuei Nukaya, Junichi Mineno, Kazutoh Takesako, Naoyuki Katayama, Hiroshi Shiku

CT and PET scan images from TCR-MA-213.



Purpose: Preparative lymphodepletion, the temporal ablation of the immune system, has been reported to promote persistence of transferred cells along with increased rates of tumor regression in patients treated with adoptive T-cell therapy. However, it remains unclear whether lymphodepletion is indispensable for immunotherapy with T-cell receptor (TCR) gene–engineered T cells.Experimental Design: We conducted a first-in-man clinical trial of TCR gene-transduced T-cell transfer in patients with recurrent MAGE-A4–expressing esophageal cancer. The patients were given sequential MAGE-A4 peptide vaccinations. The regimen included neither lymphocyte-depleting conditioning nor administration of IL2. Ten patients, divided into 3 dose cohorts, received T-cell transfer.Results: TCR-transduced cells were detected in the peripheral blood for 1 month at levels proportional to the dose administered, and in 5 patients they persisted for more than 5 months. The persisting cells maintained ex vivo antigen-specific tumor reactivity. Despite the long persistence of the transferred T cells, 7 patients exhibited tumor progression within 2 months after the treatment. Three patients who had minimal tumor lesions at baseline survived for more than 27 months.Conclusions: These results suggest that TCR-engineered T cells created by relatively short-duration in vitro culture of polyclonal lymphocytes in peripheral blood retained the capacity to survive in a host. The discordance between T-cell survival and tumor regression suggests that multiple mechanisms underlie the benefits of preparative lymphodepletion in adoptive T-cell therapy. Clin Cancer Res; 21(10); 2268–77. ©2015 AACR.

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