Determination of lymph nodes enriched in tumor reactive cells their proliferation and their use in adoptive cellular therapy

摘要

The present invention is directed to a method for reliably determining lymph nodes enriched in tumor reactive cells, e.g., CD4+tumor-specific lymphocytes. This method includes the steps of administering to a patient an effective amount of a radiolabeled locator which specifically binds a marker produced by or associated with neoplastic tissue. Time is permitted to elapse following the administration for the radiolabeled locator to preferentially concentrate in any neoplastic tissue and for unbound radiolabeled locator to be cleared, so as to increase the ratio of photon emissions from neoplastic tissue to background photon emissions in the patient. After the time has elapsed, the patient is accessed with a radiation detection probe for determining lymph node sites exhibiting accretion of the radiolabeled locator by detecting with the probe elevated levels of radiation at the lymph node sites. The lymph node sites exhibiting such elevated levels of radiation are removed and subjected to gross visual analysis, though such sites alternatively may be subjected to histological analysis. Those determined and removed lymph nodes that also are determined to be tumor-free by gross observation or free of gross metastatic disease are selected and cultured to proliferate tumor reactive cells. The selected lymph nodes are subjected to mitogenic stimulation. The lymph nodes are cultured in the presence of Interleukin-2, anti-CD3 monoclonal antibody, and neoplastic tissue which may be autologous or allogeneic tumor. The tumor reactive cells, proliferated can be used with adoptive immunotherapy regimens for mitigating the progression of tumor.