Renal Cancer Responds to Anti-CD3-Activated T Cell Vaccine

ORLANDO—Adoptive transfer of T cells taken from tumor-draining lymph nodes and secondarily activated and expanded in vitro can shrink established renal cell cancers, according to phase II data reported at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 10). Alfred E. Chang, MD, chief of the Division of Surgical Oncology, University of Michigan Health Systems, Ann Arbor, presented the study.

In earlier trials in established pulmonary metastasis animal models, the adoptive transfer of tumor-draining lymph node cells by themselves did not cause tumor regression, so methods for increasing immunogenicity were explored.

The researchers harvested autologous tumor from advanced cancer patients with melanoma and renal cell cancer, and developed a tumor vaccine consisting of irradiated tumor cells and bacillus Calmette-Guérin (BCG). They injected this vaccine intradermally into the skin of the thigh, and a week to 10 days later harvested draining lymph nodes in the groin. The lymph node cells were then activated secondarily with immobilized anti-CD3 monoclonal antibody, cultured in low concentrations of interleukin-2 (IL-2), and expanded in semipermeable bags to generate large numbers of cells for transfer back to the patient.

A pilot study of this vaccine in 11 melanoma and 12 renal cell cancer patients produced one partial response in a melanoma patient, and two partial responses and two complete responses in the renal cell patients. "This encouraged us to initiate the phase II trial," Dr. Chang said.

The phase II study using the new vaccine technique, enrolled 39 stage IV renal cell cancer patients without central nervous system metastases.

"The lymph node cells after activation were virtually all CD3-positive T cells. CD8 cells were preferentially activated during this culture period, as opposed to CD4 cells, which were decreased in number," Dr. Chang said.

The adoptive transfer was done as an inpatient procedure. The cells were given with IL-2 given concomitantly at 360,000 IU/kg every 8 hours for up to 15 doses. Patients were evaluated 1 and 2 months after treatment. Stable or responding patients were retreated with cryopreserved vaccine-primed lymph node cells.

Of 33 evaluable patients, there were 4 complete responses and 5 partial re-sponses for a 27% response rate. "Two partial response patients who had residual disease that remained stable were resected and have remained disease free," Dr. Chang said.

During the discussion period, questions were raised about whether the observed response might be due to the IL-2 alone. "It’s possible. We know that IL-2 alone at high doses will give a 15% response rate. In our second-generation study, we are considering using activated T cells alone, without the concomitant administration of IL-2," Dr. Chang said.

The researchers are also working on methods for double-activating vaccine-primed lymph node cells using conjugated antibodies.