T-cell adoptive immunotherapy of metastatic renal cell carcinoma.
OBJECTIVE
To determine the feasibility and toxicity of the adoptive transfer of ex vivo-activated T lymphocytes that have been sensitized to autologous tumor vaccine in vivo.


METHODS
Twenty patients with extensive metastatic renal cell carcinoma received systemic adoptive immunotherapy with autologous T cells in the absence of conjunctional interleukin-2 (IL-2) administration. Patients were vaccinated intradermally with irradiated autologous tumor cells and granulocyte-macrophage colony-stimulating factor as an adjuvant to stimulate an immune response. Inguinal lymph nodes draining the vaccine site were surgically removed, and the cells were stimulated with staphylococcal enterotoxin A followed by expansion in 60 IU/mL IL-2, and in some cases additionally stimulated with anti-CD3 monoclonal antibody and IL-2, to obtain a large number of cells.


RESULTS
The staphylococcal enterotoxin A/IL-2 activation induced vigorous proliferation of T cells (median expansion 26-fold) that were a mixture of CD4 and CD8 T lymphocytes. Activated cells were infused intravenously at doses ranging from 2x10(9) to 9.5x10(10). There was minimal toxicity consisting of grade 1 or 2 fever and nausea, and the entire treatment was delivered as outpatient therapy. One patient had a partial response, one had a mixed response, and 8 had stable disease lasting at least 5 months.


CONCLUSIONS
Adoptive transfer of ex vivo-activated, tumor vaccine-primed lymph node cells is feasible and is associated with minimal toxicity when used alone. These results warrant further study in a Phase II trial.
Plautz
G E
GE
Center for Surgery Research, Experimental Therapeutics Program and Department of Urology, Cleveland Clinic Foundation, Ohio, USA.
Bukowski
R M
RM
Novick
A C
AC
Klein
E A
EA
Kursh
E D
ED
Olencki
T E
TE
Yetman
R J
RJ
Pienkny
A
A
Sandstrom
K
K
Shu
S
S
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000556:secondary* / Q000628:therapy*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D007680:Kidney Neoplasms; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes