Cellular immunotherapy for patients with metastatic colorectal carcinoma using lymph node lymphocytes localized in vivo by radiolabeled monoclonal antibody

BACKGROUND. The authors showed previously that radiolabeled monoclonal anti body (MoAb) and a hand-held, gamma-detecting probe can be used to localize tumor-reactive lymph nodes in vivo. The authors examined the feasibility, s afety, and biologic effects of cellular immunotherapy using autologous cell s expanded from these lymph nodes in patients with metastatic colorectal ca rcinoma. METHODS. Tumor-reactive lymph nodes containing radiolabeled MoAb were local ized and excised from 32 patients with metastatic, unresectable colorectal carcinoma at laparotomy. Lymph nodes were dissociated, and cells were cultu red ex vivo for 10-14 days. Patients received a single infusion of autologo us, expanded cells with no systemic interleukin (IL)-2. RESULTS. A mean of 1.6 x 10(10) expanded autologous lymph node cells were i nfused with toxicity limited to occasional fevers or chills. The cells infu sed predominately were activated CD3(+) T-cells that expressed genes for IL -4, IL-5, interferon-gamma, and granulocyte-macrophage colony stimulating f actor (GM-CSF) by using reverse transcriptase-polymerase chain reaction. In dium-111 labeled cells were observed to traffic initially to the lungs, bon e marrow, liver, and spleen. One patient on study achieved a partial respon se (>80% reduction), and mixed or minor responses were noted in 4 other pat ients. The responding patient's cell characteristics were notable for high levels of GM-CSF and IL-4 secretion on restimulation with immobilized anti- CD3 in vitro, and biopsies of the tumor were characterized by macrophage in filtration. The median survival of the cell-treated group compared favorabl y with a similar group of patients who underwent radioimmunoguided surgery without cell treatment (12.5 months vs. 5.8 months). CONCLUSIONS. The infusion of cells expanded from tumor-reactive lymph nodes localized with radiolabeled MoAb in vivo is reproducible and safe and has biologic activity, even in the absence of systemic IL-2 infusion. This appr oach represents a novel application of MoAb technology, in that MoAbs are u sed not to diagnose or treat disease directly but rather to identify lymph node cells with therapeutic potential. Cancer 1999;86:22-30. (C) 1999 Ameri can Cancer Society.