Establishing a platform for immunotherapy: clinical outcome and study of immune reconstitution after high-dose chemotherapy with progenitor cell support in breast cancer patients.
Tumor vaccine after high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) aims at directing immune recovery toward tumor responses after optimizing minimal residual disease. We have characterized T-cell recovery and tumor response after a regimen devised as a platform for such immunotherapy. One hundred patients with high-risk or metastatic breast cancer received 3 to 7 cycles of paclitaxel and cyclophosphamide (overall response rate, 78%) and then HDC with melphalan and etoposide. Seventy-one patients received HDC and ASCT (no mortality at 100 days). At 24 months after transplantation, progression-free and overall survival probabilities for patients with stage IIIA, IIIB, and IV disease were 82%, 81%, and 42% and 100%, 94%, and 68%, respectively. The median progression-free and overall survivals from entry on study for stage IV patients were 15.3 and 38.1 months, respectively. CD3 + , CD8 + , and CD4 + cells were severely depleted after ASCT. Although total CD8 + T-cell numbers approached the normal range by 3 months, most of these cells were CD28 - . Naive CD45RA + CD4 + T cells approached the normal range only 18 months after ASCT and only in younger patients. The described observations provide the basis for devising a strategy for cancer vaccine administration after ASCT. Incorporating immune reconstitution enhancement after ASCT may be advantageous.
Sportès
Claude
C
Experimental Transplantation & Immunology Branch, Center for Cancer Research, National Cancer Institute, 10 Center Dr., CRC Room 43142, Bethesda, MD 20892-1203, USA. kastensc@mail.nih.gov
McCarthy
Nicole J
NJ
Hakim
Frances
F
Steinberg
Seth M
SM
Liewehr
David J
DJ
Weng
David
D
Kummar
Shivaani
S
Gea-Banacloche
Juan
J
Chow
Catherine K
CK
Dean
Robert M
RM
Castro
Kathleen M
KM
Marchigiani
Donna
D
Bishop
Michael R
MR
Fowler
Daniel H
DH
Gress
Ronald E
RE
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D020127:Recovery of Function / Q000187:drug effects / Q000276:immunology; D014182:Transplantation, Autologous; D014611:Vaccination
D019496:Cancer Vaccines