Phase I trial of a recombinant vaccinia virus encoding carcinoembryonic antigen in metastatic adenocarcinoma: comparison of intradermal versus subcutaneous administration

Authors

Robert Conry, The University of Alabama at Birmingham, USA
Muhamad Khazaeli, The University of Alabama at Birmingham, USA
Mansoor Saleh, Aga Khan UniversityFollow
Karen Allen, The University of Alabama at Birmingham, USA
Daunte Barlow, The University of Alabama at Birmingham, USA
Susan Moore, The University of Alabama at Birmingham, USA
Dayle Craig, The University of Alabama at Birmingham, USA
Ramin Arani, The University of Alabama at Birmingham, USA
Jeffrey Schlom, The University of Alabama at Birmingham, USA
Albert LoBuglio, The University of Alabama at Birmingham, USA

Document Type

Article

Department

Haematology and Oncology, East Africa

Abstract

The principal objectives of this trial were twofold: (a) to examine the safety and relative efficacy of intradermal needle injection versus s.c. jet administration of a carcinoembryonic antigen (CEA)-encoding recombinant vaccinia virus (rV-CEA) over a limited dose range and (b) to evaluate CEA-specific immune responses or antitumor effects induced by rV-CEA vaccination. Patients were randomly assigned to one of two groups, depending upon the technique of vaccine administration. All 20 patients received two doses of 10(7) or 10(8) pfu of rV-CEA at a 4-week interval. Toxicity was limited to modest local inflammation at the inoculation site as well as low-grade fever and increased fatigue, each affecting fewer than 20% of the patients. No evidence of CEA-specific lymphoproliferation, interleukin 2 release, delayed-type hypersensitivity, or antibody response was observed. Thus, the efficacy comparison between the two administration techniques was based upon the induction of immune responses to the vaccinia virus vector. Both techniques induced vaccinia-specific lymphoproliferation, interleukin 2 release, and antibody responses of comparable magnitude and frequency as well as protected 80% of patients against pustule formation following vaccinia scarification. Thus, there is no compelling reason to recommend one administration technique over the other based upon toxicity or efficacy. We have selected s.c. jet injection for subsequent trials of rV-CEA based on the ability to accommodate larger injection volumes, enhanced standardization between clinicians, and avoidance of needles that could transmit the vaccine or blood-borne pathogens to health care workers. We recommend use of 10(8) pfu doses for subsequent trials of recombinant vaccinia virus vaccines based upon the favorable toxicity profile and more consistent local pustule formation indicative of an adequate inoculation of live virus. No objective clinical responses to the rV-CEA vaccine were observed among this population of patients with widely metastatic adenocarcinoma.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Clinical cancer research

Recommended Citation

Conry, R., Khazaeli, M., Saleh, M., Allen, K., Barlow, D., Moore, S., Craig, D., Arani, R., Schlom, J., LoBuglio, A. (1999). Phase I trial of a recombinant vaccinia virus encoding carcinoembryonic antigen in metastatic adenocarcinoma: comparison of intradermal versus subcutaneous administration. Clinical cancer research, 5(9), 2330-2337.
Available at: https://ecommons.aku.edu/eastafrica_fhs_mc_haematol_oncol/104