Clinical and immunologic effects of intranodal autologous tumor lysate-dendritic cell vaccine with Aldesleukin (Interleukin 2) and IFN-{alpha}2a therapy in metastatic renal cell carcinoma patients.
OBJECTIVE
To evaluate the clinical and immunologic outcomes of DC (dendritic cell) vaccine with interleukin (IL)-2 and IFN-alpha 2a in metastatic renal cell carcinoma patients.


METHODS
Eighteen consented and eligible patients were treated. Peripheral blood monocytes were cultured ex vivo into mature DCs and loaded with autologous tumor lysate. Treatment consisted of five cycles of intranodal vaccination of DCs (1 x 10(7) cells/1 mL Lactated Ringer's solution), 5-day continuous i.v. infusion of IL-2 (18MiU/m2), and three s.c. injections of IFN-alpha 2a (6MiU) every other day. Response Evaluation Criteria in Solid Tumors criteria were used for disease assessment. Correlative immunologic end points included peripheral blood lymphocyte cell phenotype and function as well as peripheral blood anti-renal cell carcinoma antibody and cytokine levels.


RESULTS
All patients received between two and five treatment cycles. Toxicities consisted of known and expected cytokine side effects. Overall objective clinical response rate was 50% with three complete responses. Median time to progression for all patients was 8 months, and median survival has not been reached (median follow up of 37+ months). Treatment-related changes in correlative immunologic end points were noted and the level of circulating CD4(+) T regulatory cells had a strong association with outcome. Pre-IP-10 serum levels approached significance for predicting outcome.


CONCLUSIONS
The clinical and immunologic responses observed in this trial suggest an interaction between DC vaccination and cytokine therapy. Our data support the hypothesis that modulation of inflammatory, regulatory, and angiogenic pathways are necessary to optimize therapeutic benefit in renal cell carcinoma patients. Further exploration of this approach is warranted.
Schwaab
Thomas
T
Medical Oncology Immunotherapy Group, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.
Schwarzer
Adrian
A
Wolf
Benita
B
Crocenzi
Todd S
TS
Seigne
John D
JD
Crosby
Nancy A
NA
Cole
Bernard F
BF
Fisher
Jan L
JL
Uhlenhake
Jill C
JC
Mellinger
Diane
D
Foster
Cathy
C
Szczepiorkowski
Zbigniew M
ZM
Webber
Susan M
SM
Schned
Alan R
AR
Harris
Robert D
RD
Barth
Richard J
RJ
Heaney
John A
JA
Noelle
Randolph J
RJ
Ernstoff
Marc S
MS
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D054357:Chemokine CXCL10 / Q000097:blood; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
D000970:Antineoplastic Agents; C114753:CXCL10 protein, human; D019496:Cancer Vaccines; D054357:Chemokine CXCL10; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; C082598:aldesleukin