A neoadjuvant clinical trial in colorectal cancer patients of the human anti-idiotypic antibody 105AD7, which mimics CD55.
Thirty-five patients received 105AD7 human anti-idiotype vaccination prior to surgery for colorectal carcinoma. Patients were immunized before and also received one to two immunizations after surgical resection of their colorectal cancer. The vaccine was well tolerated with no associated toxicity. Lymphocytic infiltration within the resected tumors was quantified by immunohistochemistry and image analysis. Enhanced infiltration of helper T cells (CD4) and natural killer (NK) cells (CD56) were observed in the tumors from immunized patients when compared with tumors from stage, grade, site, age, and sex matched unimmunized patients. NK activity was increased in the blood, peaking 7-10 days post immunization and then dropping rapidly and correlating with NK extravasation within the tumor. Comparison of the amino acid sequences of 105AD7 anti-idiotype and the antigen it mimics, CD55, has predicted that patients with HLA-DR1, HLA-DR3, and HLA-DR7 haplotypes should show helper T cell responses following 105AD7 vaccination. Eighty-three percent of patients expressing these haplotypes responded to 105AD7, whereas 88% of patients who failed to express these haplotypes were nonresponders. With a median follow-up of 4 years (range, 2.5-6 years) 65% of patients remained disease free. This trial shows that 105AD7 stimulates antitumor inflammatory responses allowing extravasation within tumor deposits of both helper T cells and NK cells. This represents a way of evaluating immune responses in patients both within the blood and at the tumor site. The study confirms that immunization with a human anti-idiotypic antibody results in immune responses in 83% of patients with a permissive haplotype.
Durrant
L G
LG
Cancer Research Campaign Academic Unit of Clinical Oncology, University of Nottingham, United Kingdom. Lindy.durrant@nott.ac.uk
Maxwell-Armstrong
C
C
Buckley
D
D
Amin
S
S
Robins
R A
RA
Carmichael
J
J
Scholefield
J H
JH
D000888:Antibodies, Anti-Idiotypic / Q000009:adverse effects*; D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018958:CD55 Antigens / Q000276:immunology; D019496:Cancer Vaccines / Q000009:adverse effects*; D002430:Cecal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D015179:Colorectal Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D009367:Neoplasm Staging; D012004:Rectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D012811:Sigmoid Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D016019:Survival Analysis
C405618:105AD7 antibody; D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; D018958:CD55 Antigens; D019496:Cancer Vaccines; D006684:HLA-DR Antigens