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Adoptive immunotherapy of cancer using activated Autologous lymphocytes-current status and new strategies-

  • Feature … Practice of Immuno-Cell Therapy and its Future Prospect …
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Abstract

After the discovery of interleukin-2 (IL-2), lymphokine-activated killer (LAK) cells, tumor-infiltrating lymphocytes (TILs), and cytotoxic T lymphocytes (CTLs) sensitized with the mixed lymphocyte-tumor culture (MLTC) system have been conducted in adoptive immunotherapy (NT) trials during past 15 years. Although the overall response rate of tumor shrinkage was marginal (9%), locoregional administration of TILs for malignant effusions was effective (77%) for a decrease or disappearance of the effusions even in terminally-ill patients, resulting in an improvement of QOL. Recent advances for molecular understanding of antigen presentation and recognition have promoted us to enhance the efficacy of AIT by using cultured dendritic cells (DCs) for generating antigen-specsc CTLs in vitro. The peptidepulsed DC-activated killer (PDAK) cells showed tumor recognition against antigen-expressing cells, and were efficiently propagated with the IL2 plus immobilized anti-CD3 antibody (IL-2/CD3) culture system. Clinical trials using PDAK cells against patients with lung metastases are now progressed, in which peptides suitable for generating CTLs were chosen in individual patients using the method designated as host-oriented peptide evaluation (HPOE) approach. Moreover, DCs were introduced with tumor-derived RNA, which was amplied with the T7 promoter system, and then were used for stimulating lymphocytes. The tumor RNA-introduced DC-activated killer (TRiDAK) cells showed tumor-specific interferon-gamma spots even in a patient in whom we failed to generate PDAK cells using DCs and peptides, suggesting that the clinical trial of AIT using TRiDAK ceIls is warranted for the treatment of patients with metastatic cancer. Thus, more understanding of antigen-presentation and -recognition mechanisms and immune regulation systems may promote clinical applications of AIT to establish a novel modality of cancer treatment.

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Authors and Affiliations

  1. Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Yoshiyuki

    Yoshiyuki Yamaguchi, Akiko Ohshita, Yoshiharu Kawabuchi, Koji Ohta, Katsuhiko Shimizu, Kazuhito Minami, Jun Hihara, Eiji Miyahara & Tetsuya Toge

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  1. Yoshiyuki Yamaguchi
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  2. Akiko Ohshita
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  3. Yoshiharu Kawabuchi
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  4. Koji Ohta
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  5. Katsuhiko Shimizu
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  6. Kazuhito Minami
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  7. Jun Hihara
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  8. Eiji Miyahara
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  9. Tetsuya Toge
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Correspondence to Yoshiyuki Yamaguchi.

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Yamaguchi, Y., Ohshita, A., Kawabuchi, Y. et al. Adoptive immunotherapy of cancer using activated Autologous lymphocytes-current status and new strategies-. Hum Cell 16, 183–189 (2003). https://doi.org/10.1111/j.1749-0774.2003.tb00152.x

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  • DOI: https://doi.org/10.1111/j.1749-0774.2003.tb00152.x

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