Generation of vaccine-primed lymphocytes for the treatment of head and neck cancer.
BACKGROUND
This study was performed to assess the ability of autologous tumor vaccines to induce T-cell reactivity to squamous cell cancers (SCC).


METHODS
Irradiated autologous tumor cells admixed with bacillus Calmette-Guérin (BCG) were given intradermally in patients with advanced head and neck cancers. Vaccine-primed lymph node (VPLN) cells were secondarily activated with anti-CD3 mAb and expanded in IL-2 for adoptive immunotherapy. A mean (+/- SEM) of 2 (+/-0.6) x 10(10) anti-CD3-activated cells were administered in conjunction with IL-2 in six patients.


RESULTS
Anti-CD3-activated VPLN cells secreted IFN-gamma and GM-CSF in response to autologous tumor cells but not to allogeneic tumor cells in four of five patients analyzed. Both CD4(+) and CD8(+) tumor reactive cells were present in the VPLN. There were no significant tumor responses after transfer of the anti-CD3-activated VPLN. In separate experiments, costimulation of VPLN cells with anti-CD3 and anti-CD28 mAb resulted in enhanced cytokine secretion to autologous tumor compared with anti-CD3 activation alone.


CONCLUSIONS
Both CD4(+) and CD8(+) responses can be induced to SCC by autologous tumor vaccination. However, additional approaches need to be identified to enhance the therapeutic efficacy of this approach.
Chang
Alfred E
AE
Division of Surgical Oncology, 3302 Cancer Center, 1500 E. Medical Center Drive, Ann Arbor, Michigan 48109, USA.
Li
Qiao
Q
Jiang
Guihua
G
Teknos
Theodoros N
TN
Chepeha
Douglas B
DB
Bradford
Carol R
CR
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D019264:Adoptive Transfer; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D001707:Biopsy, Needle; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000276:immunology; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010166:Palliative Care / Q000379:methods*; D010641:Phenotype; D011379:Prognosis; D011446:Prospective Studies; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D019452:Terminally Ill; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D019496:Cancer Vaccines; D016207:Cytokines; D007376:Interleukin-2