Combination therapy of renal cell carcinoma or breast cancer patients with dendritic cell vaccine and IL-2: results from a phase I/II trial.
BACKGROUND
Ten cancer patients (Six renal cell carcinoma and four breast cancer patients) were treated in a phase I/II study with a vaccine composed of autologous dendritic cells (DCs) and IL-2 to evaluate the DC vaccine-related toxicity and antigen-specific immune alteration.


METHODS
Cancer patients were treated twice with autologous CD34+ hematopoietic stem cell-derived, GM-CSF/IFN-γ-differentiated DCs pulsed with autologous tumor lysate and KLH, by 4-week interval. Following each subcutaneous injection of therapeutic DCs, low-dose (200 MIU) IL-2 was introduced for 14 consecutive days as an immune adjuvant. To determine the DC vaccine-induced immunological alterations, the KLH-specific lymphocyte proliferation, number of IFN-γ secreting T cells (ELISPOT assay), NK activity and the cytokine modulation were measured.


RESULTS
Cultured-DCs expressing HLA-DR, CD11c, CD83, and B7.1/B7.2 produced IL-12p70. After vaccination, the patients tolerated it. Clinical response was observed in one RCC patient as stable disease. However DC-vaccine related antigen-specific immune responses including peripheral blood lymphocyte proliferation and the number of IFN-r secreting cells were induced in six patients without clear correlation with clinical responses. Also NK activity was induced significantly in six patients after vaccination. DC vaccine-related decrease of TGF-β level or increase of IL-12p70 level and decline of CD4+CD25+ T cells were observed in three patients. However only in the RCC patient whose disease stabilized, combination of stimulatory as well as inhibitory immune alterations including induction of IFN-γ secreting T cell with reduction of CD4+ CD25+ T cell were correlated with clinical responses.


CONCLUSIONS
Data indicated that DC vaccine combined with IL-2 is well tolerated without major side effects. DC vaccine induced the specific immunity against introduced antigen. Combinatorial alterations of immunological parameters indicating antigen-specific immune induction along with reduction of inhibitory immunity were correlated with clinical responses in DC vaccine treated patients.
Office of Biomedical Research, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Soyoung
S
Baek
Choung-Soo
CS
Kim
Sung-Bae
SB
Kim
Yong-Man
YM
Kim
Seog-Woon
SW
Kwon
YongMan
Y
Kim
Hyunsoo
H
Kim
Hyunah
H
Lee
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology*; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D055815:Young Adult
D019496:Cancer Vaccines; D000939:Epitopes; D007376:Interleukin-2; D007371:Interferon-gamma