Treatment of kidney cancer with autologous tumor cell vaccines of short-term cell lines derived from renal cell carcinoma.
BACKGROUND
We established short-term cultures of autologous tumors from patients with renal carcinoma for use as active specific immunotherapy (i.e., autologous vaccine).


METHODS
Between 9/91 and 9/99 the cell biology laboratory of the Hoag Cancer Center received 69 kidney tumor samples that had been surgically excised, including 43 primary tumors and 26 metastatic lesions. Efforts were made to establish short-term tumor cell cultures to use as autologous tumor cell vaccines. Prior to treatment, patients underwent a baseline skin test for delayed tumor hypersensitivity (DTH) and then received s.c. injections of 10 million irradiated tumor cells that were given with various adjuvants weekly x3 and then monthly x5.


RESULTS
Cell lines were established for 55/69 patients (80%) including 36/43 (84%) from primary tumors and 19/26 (73%) from distant metastases. Vaccines were prepared for 41 patients; 27 were treated. At the time of this analysis, follow up data was available for 26 patients with a median follow up > 5 years. Treatment was well-tolerated. Of 10 patients who had no evident disease at the time of treatment, nine were alive 1-8 years later; 5/8 had conversion of their DTH test from negative to positive. For 16 patients with measurable metastatic disease at the time of treatment, there were no objective tumor responses; their median survival was 5.0 months. Among these 16 patients, only 1/8 DTH tests converted, but three had a positive baseline DTH test; one was previously treated with interleukin-2 and tumor infiltrating lymphocytes and two others were previously treated with autolymphocyte therapy.


CONCLUSIONS
Vaccine therapy with short-term cultures of autologous tumor cells is feasible, well-tolerated and associated with conversion of DTH and long-term survival in patients who are free of disease at the time treatment is initiated. However, significant anti-tumor responses were not seen in patients with measurable disease at the time vaccine treatment was initiated.
Hoag Cancer Center, One Hoag Drive, Building 41, Newport Beach, California 92658, USA. rdillman@hoaghospital.org
R O
RO
Dillman
N M
NM
Barth
L A
LA
VanderMolen
D H
DH
Garfield
C
C
De Leon
A A
AA
O'Connor
K
K
Mahdavi
S K
SK
Nayak
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007114:Immunization; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007371:Interferon-gamma / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009392:Nephrectomy; D011994:Recombinant Proteins; D016019:Survival Analysis; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000276:immunology
D001500:BCG Vaccine; D019496:Cancer Vaccines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; C081222:sargramostim; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide