Trial Information

Phase I/II Clinical Trial for the Evaluation of the Interaction Between Chemotherapy and Immunotherapy in Melanoma Patients

Recently, it is becoming increasingly accepted that, in order to induce a clinically
effective antitumor response, immunotherapy needs to be combined with chemotherapy. Thus,
the traditional perception that chemotherapy and immunotherapy act through unrelated
mechanisms which may be antagonistic is challenged on the premises that a selected panel of
drugs can induce an immunogenic cell death producing specific danger signals. Furthermore,
chemotherapy combined to immunotherapy may affect antigen cross-presentation, induce a
"cytokine storm", reduce the number of regulatory T cells and activate homeostatic lymphoid
proliferation. Our previous results obtained in a mouse model, demonstrated that
drug-induced cytokines can favour antitumor immunity. Based on this observation, we explored
whether the administration of dacarbazine (DTIC) in disease-free melanoma patients in
combination with peptide vaccination could result into an improved anti tumor immune
response.

Patients included in the study were assigned to two treatment arms either receiving
anti-tumor vaccination with Melan-A and gp100 analog peptides alone (arm 1) or in
combination with DTIC pre-treatment (arm 2).

Arm 1, vaccine alone: patients received i.d. injections of Melan-A: 26-35 (A27L) and gp100:
209-217 (210M) peptides (250 µg each) formulated in Montanide ISA-51 plus s.c. injection of
3MU IFN-α, as an adjuvant on day 1 and 8 every 21 days for a total of 5 courses (10
vaccinations). Both peptides and IFN-α were injected in close but separate sites next to
local lymph nodes.

Arm 2, DTIC plus vaccine: the same vaccination schedule was combined with DTIC (800 mg/mq
i.v.) administered one day before each vaccine administration according to the standard
treatment.