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

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.

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