Localization of tumor-reactive lymph node lymphocytes in vivo using radiolabeled monoclonal antibody

Abstract

Background. Lymph node lymphocytes vary in their responsiveness to tumor. A technique has been developed that uses radiolabeled monoclonal antibody (MoAb) against the tumor‐associated mucin, TAG‐72, and a gamma‐detecting probe by which lymph nodes containing microscopic tumor and/or shed TAG‐72 can be identified in vivo. The immunologic characteristics of these lymph nodes were examined. Methods. Patients with colon cancer received 125I‐labeled MoAb CC49 by intravenous injection preoperatively. During laparotomy lymph nodes that appeared normal on inspection and palpation but which contained radiolabeled MoAb were identified using a hand‐held gamma‐detecting probe. These lymph nodes and other lymph node and tumor specimens were resected for analysis. Results. Lymph nodes identified by the probe were found by immunohistochemical studies to contain microscopic tumor and/or shed antigen associated with germinal centers. They were characterized by greater CD4+:CD8+ ratios, rates of expansion, and cytolytic activity compared with lymphocytes from lymph nodes with macroscopic tumor, noninvolved lymph nodes, and tumors. All lymph node lymphocytes identified by the probe demonstrated significant proliferative responses to autologous tumor and, in contrast to lymphocytes from noninvolved lymph nodes, significant proliferative responses to allogeneic TAG‐72+ tumor cells and to soluble TAG‐72+ mucin. Conclusions. By locating lymph nodes with microscopic tumor and/or shed antigen, the use of radiolabeled MoAb in vivo can be used to reproducibly identify tumor‐reactive lymph node lymphocytes. This technique may be useful in identifying cells for use in adoptive immunotherapy programs and in studying the regulation of immune responses in vivo.

Intratumoral injection of dendritic cells derived in vitro in patients with metastatic cancer

“…17 Mechanically disaggregated samples of tumor tissue were placed into culture for 48 hours (standardized to 10 6 cells) in modified AIM V. After 48 hours, they were cultured with 100 IU/mL of human recombinant IL-2 (Cetus, Emeryville, CA) for 7-10 days. Tumor cells and DCs were then separated by brief (20-minute) centrifugation on a discontinuous Percoll gradient.…”

Experimental radioimmunoguided surgery for peritoneal metastases of gastric cancer using anticarcinoembryonic antigen-specific T84.66 F(ab’)2

“…This may be due to the innate difference between the two procedures and to the denaturation of cross-linking proteins during formalin fixation. Background radioactivity in vivo may be due to binding of probe to membrane CEA on nontumor cells (Triozzi et al 1994), freely circulating agent, and dissociated radionuclides. Since we found that immunostaining was weak or nonexistent in organs without tumor cells, the first type of background radioactivity was not detected in our study.…”

Educational Review Cellular and Biological Therapies of Gastrointestinal Tumors: Overview of Clinical Trials

“…In this technique, 125 I-labeled CC49, a murine monoclonal antibody that targets the tumor associated antigen TAG-72, 36 is injected pre-operatively and at the time of laparotomy, a hand-held radiation detecting probe 37 is used to identify lymph nodes containing this antigen. 38 Interestingly, this technique can identify grossly tumor-free lymph nodes which contain lymphocytes that proliferate specifically in response to autologous tumor cells, allogeneic TAG-72 ϩ tumor cells, and soluble mucin possessing the TAG-72 epitope. 38,39 These lymphocytes secrete cytokines and are non-cytolytic.…”

“…38 Interestingly, this technique can identify grossly tumor-free lymph nodes which contain lymphocytes that proliferate specifically in response to autologous tumor cells, allogeneic TAG-72 ϩ tumor cells, and soluble mucin possessing the TAG-72 epitope. 38,39 These lymphocytes secrete cytokines and are non-cytolytic. A phase I study in patients with unresectable metastatic colorectal cancer has been performed in which lymphocytes derived from resected, RIGS-localized lymph nodes were cultured ex vivo and reinfused as activated cell therapy (ACT).…”