Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells.
OBJECTIVE
We wanted to evaluate feasibility and safety of dendritic cell-based immunotherapy in patients with metastatic renal cell carcinoma (RCC).


METHODS
Patients with metastatic RCC (n = 35) received vaccinations (i.v. or i.d.) of CD83+ autologous monocyte-derived dendritic cells (moDCs). MoDCs were loaded with lysate of cultured autologous or allogeneic permanent tumor cells (A-498) as well as keyhole limpet hemocyanin as control and helper antigen. Maturation of moDCs was induced by a combination of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, and prostaglandin E2.


RESULTS
Treatment was associated with transient flu-like symptoms. In 2 of 27 evaluable patients, any evidence of disease disappeared (complete response). In both cases, metastatic tissue had been the source of tumor antigen. One patient had an objective partial response. Seven patients had stable disease, the remaining 17 patients had progressive disease. In 11 of 11 patients evaluated, moDCs induced strong immune responses against keyhole limpet hemocyanin. In 5 of 6 patients tested, enhanced immune responses against oncofetal antigen (immature laminin receptor; OFA/LRP) could also be detected. The strongest responses against OFA/LRP were detectable in 2 patients with complete response and partial response, respectively. At the time of submission, mean follow up is 32 months and 8 patients are currently alive.


CONCLUSIONS
Our data indicate that moDC-based vaccination is well tolerated and has immunological as well as clinical effects in patients with metastatic RCC. OFA/LRP might be an attractive candidate antigen for DC-based immunotherapy of RCC.
Höltl
Lorenz
L
Department of Urology, University of Innsbruck, 6020 Innsbruck, Austria.
Zelle-Rieser
Claudia
C
Gander
Hubert
H
Papesh
Christine
C
Ramoner
Reinhold
R
Bartsch
Georg
G
Rogatsch
Hermann
H
Barsoum
Adel L
AL
Coggin
Joseph H
JH
Thurnher
Martin
M
D000328:Adult; D000368:Aged; D015703:Antigens, CD; D002292:Carcinoma, Renal Cell / Q000473:pathology / Q000628:therapy*; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006433:Hemocyanins / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007150:Immunohistochemistry; D007167:Immunotherapy; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007680:Kidney Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009362:Neoplasm Metastasis; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097802:CD83 Antigen
D015703:Antigens, CD; D016207:Cytokines; D015232:Dinoprostone; D006433:Hemocyanins; D007136:Immunoglobulins; D007375:Interleukin-1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen; C032808:keyhole-limpet hemocyanin