Genetically modified T lymphocytes: More than just direct effectors

Evaluation of: Russo V, Pilla L, Lunghi F et al. Clinical and immunologic responses in melanoma patients vaccinated with MAGE-A3-genetically modified lymphocytes. Int. J. Cancer 132(11), 2557-2566 (2012). When one mentions T lymphocytes, one easily recognizes the effective and antigen-specific manner by which T lymphocytes execute cellular immune responses towards pathogen-infected or cancerous cells. Russo and coworkers recognized the other side of the coin and exploited the potency of T cells to act as a cellular vaccine, to which end they used T cells transduced with the cancer-testis antigen MAGE-A3. Twenty-three patients with MAGE-A3-expressing melanoma were treated and six patients developed MAGE-A3-specific immune responses and showed clinical benefit, whereas patients without a MAGE-A3-specific immune response did not show clinical benefit. This report includes and extends on results from a pilot study including ten patients, of which three developed MAGE-A3-specific immune responses. The present study further explores a potential beneficial application of the observed immunogenicity of genetically modified T cells.

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