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 antibody (MoAb) and a hand-held, gamma-detecting probe can be used to localize tumor-reactive lymph nodes in vivo. The authors examined the feasibility, safety, and biologic effects of cellular immunotherapy using autologous cells expanded from these lymph nodes in patients with metastatic colorectal carcinoma.


METHODS
Tumor-reactive lymph nodes containing radiolabeled MoAb were localized and excised from 32 patients with metastatic, unresectable colorectal carcinoma at laparotomy. Lymph nodes were dissociated, and cells were cultured ex vivo for 10-14 days. Patients received a single infusion of autologous, expanded cells with no systemic interleukin (IL)-2.


RESULTS
A mean of 1.6 x 10(10) expanded autologous lymph node cells were infused with toxicity limited to occasional fevers or chills. The cells infused predominately were activated CD3+ T-cells that expressed genes for IL-4, IL-5, interferon-gamma, and granulocyte-macrophage colony stimulating factor (GM-CSF) by using reverse transcriptase-polymerase chain reaction. Indium-111 labeled cells were observed to traffic initially to the lungs, bone marrow, liver, and spleen. One patient on study achieved a partial response (>80% reduction), and mixed or minor responses were noted in 4 other patients. 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 infiltration. The median survival of the cell-treated group compared favorably 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 approach represents a novel application of MoAb technology, in that MoAbs are used not to diagnose or treat disease directly but rather to identify lymph node cells with therapeutic potential.
Kim
J A
JA
The Arthur G. James Cancer Hospital and Research Institute/The Ohio State University Comprehensive Cancer Center, Columbus, USA.
Bresler
H S
HS
Martin
E W
EW
Aldrich
W
W
Heffelfinger
M
M
Triozzi
P L
PL
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017252:CD3 Complex; D015179:Colorectal Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D008198:Lymph Nodes / Q000166:cytology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy; D016019:Survival Analysis; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007376:Interleukin-2