A neoadjuvant/adjuvant randomized trial of colorectal cancer patients vaccinated with an anti-idiotypic antibody, 105AD7, mimicking CD55.
OBJECTIVE
To assess the tolerability and effectiveness of 105AD7 vaccination in colorectal cancer patients. 105AD7 is a human anti-idiotypic antibody mimicking CD55, a glycoprotein, which is more than expressed on colorectal cancer cells and protects them from attack by complement.


METHODS
Colorectal cancer patients (n = 67) eligible for primary surgery were randomized to receive the anti-idiotypic antibody 105AD7+/-Bacillus Calmette-Guerin/alum or to no treatment (control group). The immunizations were given i.d./i.m. before surgery and continued for a period of 2 years. The patients were monitored in enzyme-linked immunospot (ELISPOT; gamma-IFN), proliferation assay, and Luminex cytokine assays.


RESULTS
No serious adverse events were recorded. Of the 32 investigated immunized patients, 14 (44%) were considered to be responders in the ELISPOT assay. Induced proliferative responses were noted in 17 of 40 (43%) monitored patients. There was no correlation between the ELISPOT and proliferation assays. Luminex analyses revealed tumor necrosis factor-alpha and granulocyte macrophage colony-stimulating factor responses not only to the vaccine but also toward the native antigen CD55 in 9 of 13 (69%) patients.


CONCLUSIONS
Immune responses to vaccination were induced in a majority of monitored patients measured by ELISPOT and proliferation assay. The lack of correlation between the ELISPOT and proliferation assays may reflect the fact that the two methods measure different T-cell responses and highlights the importance of multiple readouts in evaluating a potential cancer vaccine. Responses to both the anti-idiotype and the CD55 antigen were measurable, adding support to the use of CD55 as a target in cancer treatment.
Ullenhag
Gustav J
GJ
Academic Department of Clinical Oncology, Nottingham City Hospital, Nottingham, United Kingdom.
Spendlove
Ian
I
Watson
Nicholas F S
NF
Indar
Adrian A
AA
Dube
Mukul
M
Robins
Richard A
RA
Maxwell-Armstrong
Charles
C
Scholefield
John H
JH
Durrant
Lindy G
LG
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D018958:CD55 Antigens / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002277:Carcinoma / Q000276:immunology / Q000628:therapy*; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D007371:Interferon-gamma / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018716:Molecular Mimicry / Q000276:immunology; D020360:Neoadjuvant Therapy; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
C405618:105AD7 antibody; D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D018958:CD55 Antigens; D019496:Cancer Vaccines; D016207:Cytokines; D007371:Interferon-gamma