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Radiosensitive Barrier to T-Cell-mediated Adoptive Immunotherapy of Established Tumors¹

Trudeau Institute, Saranac Lake, New York 12983

This study shows that it is not possible to cause regression of the immunogenic SA-1 sarcoma by adoptive immunotherapy with tumor-sensitized T-cells, unless the tumor-bearing recipient is exposed to a sublethal dose of -irradiation to remove a barrier that prevents adoptive immunity from being expressed. This barrier to adoptive immunotherapy was found to be regenerated between 2 and 4 weeks following irradiation, and its regeneration was associated with general repopulation of host T-cells. However, it was not regenerated in the absence of the thymus, thus showing that it is T-cell dependent. Evidence that it is caused by the presence of CD4⁺ suppressor T-cells was shown by the finding that it can be removed by depleting mice of CD4⁺ T-cells with anti-L3T4 monoclonal antibodies, but not by depleting them of CD8⁺ T-cells with anti-Lyt-2 monoclonal antibodies. Again, the barrier could be restored to irradiated recipients by infusing them with CD4⁺ T-cells, but not with CD8⁺ T-cells, from tumor-bearing donors. The barrier to adoptive immunotherapy was found to be tumor induced and to be paradoxically generated in concert with host concomitant immunity.

¹ The study was supported by Grants CA-16642 and CA-27794 from the National Cancer Institute and a grant from the Oliver S. and Jennie R. Donaldson Trust.

² To whom requests for reprints should be addressed, at the Trudeau Institute, Immunobiological Research Laboratories, P. O. Box 59, Saranac Lake, NY 12983.

Received 10/18/89. Revised 1/ 4/90.

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