Vaccination of colorectal cancer patients with modified vaccinia ankara encoding the tumor antigen 5T4 (TroVax) given alongside chemotherapy induces potent immune responses.
OBJECTIVE
The attenuated strain of vaccinia virus, modified vaccinia Ankara (MVA) encoding the tumor antigen 5T4 (TroVax), has been evaluated in an open-label phase II study in metastatic colorectal cancer patients. The primary objective was to assess the safety and immunogenicity of TroVax injected before, during, and after treatment with cycles of 5-fluorouracil, folinic acid, and oxaliplatin.


METHODS
TroVax was administered to 17 patients with metastatic colorectal cancer. In total, 11 patients were considered to be evaluable for assessment of immunologic responses having received a total of six injections of TroVax, administered before, during, and following completion of chemotherapy. Antibody and cellular responses specific for 5T4 and MVA were monitored throughout the study.


RESULTS
Administration of TroVax alongside 5-fluorouracil, folinic acid, and oxaliplatin was safe and well tolerated with no serious adverse events attributed to TroVax. Ten of the 11 evaluable patients mounted 5T4-specific antibody responses with titers ranging from 10 to >1,000. IFNgamma enzyme-linked immunospot responses specific for 5T4 were detected in 10 patients with precursor frequencies exceeding 1 in 1,000 peripheral blood mononuclear cells in 4 patients. Of the 11 evaluable patients, 6 had complete or partial responses. 5T4-specific immune responses, but not MVA-specific immune responses, correlated with clinical benefit.


CONCLUSIONS
Potent 5T4-specific cellular and/or antibody responses were induced in all evaluable patients and were still detectable during the period in which chemotherapy was administered. These results suggest that TroVax can be added to chemotherapy regimens without any evidence of enhanced toxicity or reduced immunologic efficacy and may provide additional clinical benefit.
Oxford BioMedica (UK) Ltd., The Medawar Centre, Oxford, United Kingdom. r.harrop@oxfordbiomedica.co.uk
Richard
R
Harrop
Noel
N
Drury
William
W
Shingler
Priscilla
P
Chikoti
Irina
I
Redchenko
Miles W
MW
Carroll
Susan M
SM
Kingsman
Stuart
S
Naylor
Alan
A
Melcher
Joanna
J
Nicholls
Harpreet
H
Wassan
Nagy
N
Habib
Alan
A
Anthoney
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000556:secondary / Q000628:therapy; D008207:Lymphatic Metastasis; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D014057:Tomography, X-Ray Computed; D014611:Vaccination; D019444:Vaccines, DNA; D014616:Vaccinia virus / Q000235:genetics*
D019496:Cancer Vaccines; D008562:Membrane Glycoproteins; D009944:Organoplatinum Compounds; C504058:TroVax; D019444:Vaccines, DNA; C063709:trophoblastic glycoprotein 5T4, human; D000077150:Oxaliplatin; D005472:Fluorouracil