Autologous cell vaccine as a post operative adjuvant treatment for high-risk melanoma patients (AJCC stages III and IV)

Abstract

This study evaluates the overall survival and disease free survival of melanoma patients that were treated with an autologous melanoma cell vaccine, administered as a post-operative adjuvant. Included are 43 patients with totally resected metastatic melanoma (28-AJCC stage III, 15-AJCC stage IV), with a median follow up of 34 months (6 -62). The treatment consisted of eight doses of a vaccine made of 10 -25610 6 autologous melanoma cells either released from the surgical specimen or grown in cell cultures. Tumour cells were conjugated with hapten dinitrophenyl, mixed with Bacille Calmette Guérin and irradiated to 110 Gy. Both disease free survival and overall survival were found to be correlated with intensity of evolving delayed type hypersensitivity to subcutaneous injection of unmodified melanoma cells. Patients with a delayed type hypersensitivity reaction of 510 mm had a median disease free survival of 17 months (mean 35 months) and a mean overall survival of 63 months (median not reached). In contrast, patients with a negative or weak delayed type hypersensitivity had a median disease free survival of 9 months (relative risk of recurrence=4.5, P=0.001), and a median overall survival of 16 months (relative risk of death=15, P=0.001). Stage III patients with a positive delayed type hypersensitivity reaction had an improved disease free survival of 16 months and a mean overall survival of 38 months, whereas patients with a negative delayed type hypersensitivity had a median disease free survival of 7 months (relative risk=4.5, P=0.02) and a median overall survival of 16 months (relative risk=9.5, P=0.005). The adjuvant administration of autologous melanoma vaccine was associated with improved disease-free and overall survival to selected patients who successfully attained anti-melanoma reactivity as detected by positive delayed type hypersensitivity reactions to unmodified melanoma cells.

Interleukin-2 improves tumour response to DNP-modified autologous vaccine for the treatment of metastatic malignant melanoma

“…None of the patients who failed to demonstrate a positive DTH response had any objective tumour regressions, even with the addition of IL-2. In a previous study, we found a significant correlation between the development of strong positive DTH and (Lotem et al, 2002). Similar findings were reported by Berd et al (1990Berd et al ( , 2001 and Baars et al (2000).…”

“…They developed, however, recurrence in the midst of the adjuvant protocol (between vaccines 4 and 8; three patients) or within 2 years from its initiation (four patients). These seven patients were described elsewhere before (Lotem et al, 2002). They are included in the present series because they continued vaccination in the presence of active metastatic disease or were referred for successive IL-2 therapy.…”

Autologous Melanoma Vaccine Induces Antitumor and Self-Reactive Immune Responses That Affect Patient Survival and Depend on MHC Class II Expression on Vaccine Cells

“…All patients gave their informed consent to be included in the vaccination studies. The melanoma cell lines were established as described (15). To assure melanocytic progeny, the expression of S100, MART-1, and gp100 were evaluated by immunostaining using polyclonal rabbit anti-S100, monoclonal A-103, and HMB-45 antibodies, respectively (Dako).…”

“…Before vaccination, an appropriate amount of Bacillus Calmette-Guerin was added, starting with a dilution of 1:50 and reaching 1:500, according to the resulting granuloma at the injection site. The vaccination procedure was carried out as described (15,17). On day 1, patients received 300 mg/m 2 of i.v.…”

Capture of Tumor Cell Membranes by Trogocytosis Facilitates Detection and Isolation of Tumor-Specific Functional CTLs

“…Following incubation for 1 to 5 h at 37jC, cells were washed twice in PBS containing 0.5 mmol/L EDTA, to ensure conjugate dissociation, resuspended in PBS supplemented with 0.5% bovine serum albumin and 0.1% sodium azide, and stained with FITC-conjugated or PE-Cy5-conjugated or APC-conjugated anti-human CD8 and/or CD4 (eBioscience), CD107a (BD PharMingen), or isotype control mAbs. For specific TCR staining, cells were incubated with FITC-conjugated HLA-A*0201-MART-1 [26][27][28][29][30][31][32][33][34][35] or HLA-A*0201-gp100 154-162 dextramers (Dako) for 30 min at 4jC. The samples were washed and analyzed by FACScan and ''FCS Express'' software (De Novo).…”