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

摘要

Broadly, the present invention in one aspect is directed to a method for reliably determining lymph nodes enriched in tumor reactive cells, e.g., CD4+ tumor-specific lymphocytes, often called T-helper cells or T-helper 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, e.g. cancer. Time then 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 (e.g. preferably, surgically; note: use of a laproscope may be impractical, though use of such instruments is not precluded in the present invention) 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 then are removed and subjected to gross visual analysis, though such sites alternatively/additionally may be subjected to histological analysis, e.g. hematoxylin and eosin (H&E) histologic evaluation. Those determined and removed lymph nodes that also are determined to be tumor-free by gross observation or free of gross metastatic disease (i.e., those lymph nodes that visually appear normal, but which take-up antibody) then are selected and cultured to proliferate tumor reactive cells, e.g., tumor-specific T lymphocytes therein. The selected lymph nodes are subjected to mitogenic stimulation. Advantageously, then, the lymph nodes are cultured in the presence of, for example, Interleukin-2 (IL-2), anti-CD3 monoclonal antibody, and, optionally, neoplastic tissue which may be autologous or allogeneic tumor. The tumor reactive cells, e.g., T lymphocytes, proliferated then can be used in accordance with adoptive immunotherapy regimens for mitigating (moderating) the progression of tumor. The expanded or proliferated tumor reactive cells, e.g., T lymphocytes, are an effective therapeutic agent in the treatment of cancer.