Avipox viruses are replication-defective members of the poxvirus family. Avipox-derived vectors such as ALVAC (canarypox) and
fowlpox have the ability to infect mammalian cells, including human cells, but do not replicate. The first clinical trial of an avipox
recombinant vaccine for patients with advanced
carcinomas has recently been conducted using the ALVAC vector and the human
carcinoembryonic antigen (CEA) transgene (designated ALVAC-CEA; J. L. Marshall et al, J. Clin. Oncol., 17: 332-337, 1999). The T-cell responses elicited by patients before and after vaccination with the ALVAC-CEA recombinants are characterized in this report. Pre- and postvaccination peripheral blood mononuclear cells (PMBCs) of the eight patients positive for HLA-class I A2 allele, were incubated with the HLA-A2-CEA
peptide CAP-1 and
interleukin 2. In no cases using prevaccination PMBCs could cultures be established that had the ability to lyse C1R-A2 target cells pulsed with the CAP-1
peptide. However, T-cell cultures from seven of eight of these same patients, obtained from PBMCs after ALVAC-CEA vaccination, were shown to lyse C1R-A2 cells only when pulsed with CAP-1. Moreover, all seven of these T-cell cultures were shown to lyse allogeneic human
carcinoma cell lines (SW1463 and SW480) that were both A2+ and expressed CEA; an allogeneic tumor cell line (LS174T) expressing CEA that was negative for A2 expression was not lysed. HLA-A2+ and CEA+ autologous
tumor cells were also capable of being lysed by CEA-specific T cells from this patient. Analysis of this CTL line also revealed the expression of several homing and adhesion-associated molecules. Fluorescence-activated cell sorter analysis of the T-cell lines established from patients after ALVAC-CEA vaccination revealed that most were CD8+/CD4-, but many also had a CD8+/CD4+ component. Analyses of
T-cell receptor Vbeta usage of several of the CEA-specific CTL lines showed a relatively diverse Vbeta pattern. These studies demonstrate for the first time the ability to vaccinate
cancer patients with an avipox recombinant and derive T cells that are capable of lysing allogeneic and autologous
tumor cells in a MHC-restricted manner. These studies thus form the rationale to use such replication-deficient
recombinant vaccines in future
cancer vaccine trials.