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 als o received one to two immunizations after surgical resection of their color ectal cancer. The vaccine nas well tolerated with no associated toxicity. L ymphocytic infiltration within the resected tumors was quantified by immuno histochemistry 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. Sii activity was increased in the bl ood, peaking 7-10 days post immunization and then dropping rapidly and corr elating with NK extravasation within the tumor. Comparison of the amino aci d sequences of 105AD7 anti-idiotype and the antigen it mimics, CD55, has pr edicted that patients with HLA-DR1, HLA-DR3, and HLA-DR7 haplotypes should show helper T tell responses following 105AD7 vaccination. Eighty-three per cent of patients expressing these haplotypes responded to 105AD7, whereas 8 8% of patients who faded to express these haplotypes were nonresponders. Wi th a median follow-up of 4 years (range, 2.5-6 years) 65% of patients remai ned disease free. This trial shows that 105AD7 stimulates antitumor inflamm atory 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 confirm s that immunization with a human anti-idiotypic antibody results in immune responses in 83% of patients with a permissive haplotype.