Patients treated with a monoclonal antibody (ab1) to the colorectal carcinoma antigen 17-1A develop a cellular response (DTH) to the "internal image of the antigen" (ab2).
The anti-tumor effector functions of unconjugated MAb in cancer therapy are not fully understood. Direct cytotoxic mechanisms have been demonstrated as well as induction of anti-idiotypic (ab2) and anti-anti-idiotypic (ab3) antibodies. If such a humoral response is induced, then an idiotypic cellular response would also be anticipated. Human monoclonal ab2s which mimic a tumor-associated antigen (TAA) (CO17-1A) of colorectal carcinoma (CRC) cells ("the internal image of the antigen") were produced. These ab2s were injected intradermally to patients with metastatic CRC who had been treated with the anti-colon carcinoma MAb 17-1A (ab1). Five out of 12 patients had a specific DTH (delayed-type hypersensitivity) reaction of the tuberculin type, which was proven by immunohistochemical analysis of skin biopsies. Serum ab3 was demonstrated in 4/4 tested DTH+ patients and also in 4 DTH patients. Control patients did not show any skin reactivity. Generation of an idiotypic response induced by the infused antibody (ab1) might be regarded as an active anti-tumor "vaccination". Induction of an idiotypic cellular and humoral cascade might be an important anti-tumor effector function of MAb and should be considered in future strategies for such therapy in cancer patients.
Mellstedt
H
H
Department of Oncology (Radiumhemmet), Karolinska Hospital, Stockholm, Sweden.
Frödin
J E
JE
Biberfeld
P
P
Fagerberg
J
J
Giscombe
R
R
Hernandez
A
A
Masucci
G
G
Li
S L
SL
Steinitz
M
M
D000888:Antibodies, Anti-Idiotypic / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D006968:Hypersensitivity, Delayed; D008297:Male; D012004:Rectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012867:Skin / Q000276:immunology / Q000473:pathology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; C050928:carcinoma-associated antigen 17-1A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor