A phase I trial of combination therapy of tumor lysate-pulsed dendritic cells and adoptive transfer of anti-CD3 activated T cells (TP-DC/CAT) in patients with advanced gastrointestinal (GI) cancers

Abstract

2585 Background: We have previously shown that tumor lysate-pulsed DC vaccination (TP-DC) elicited therapeutic rejection of established tumor in animal models. Administration of activated T cells was also shown to inhibit tumor relapse in patients (pts) with hepatocellular carcinoma (HCC) after curative operation. In addition, combination of TP-DC with administration of activated T cells elicited more significant therapeutic rejection of established tumor than the single therapy alone in animal models. We therefore sought to examine the therapeutic potency of TP-DC with administration of anti-CD3 activated T cells (CAT) against GI cancers: 3 pts were diagnosed with pancreatic cancer, 7 pts with HCC, 3 pts with intrahepatic cholangiocarcinoma, 2 pts with esophageal sarcoma, 12 pts with colorectal cancer. Methods: Monocyte-derived DC was generated in serum-free medium containing GM-CSF (100 ng/ml) and IL-4 (50 ng/ml). Pts received TP-DC intradermally (i.d.) 4 times every 3 weeks with 1 x 109 CAT activated with interleukin-2 and antibody to CD3: 4 pts received 1 x 106 DC, 7 received 2 x 107, 16 received 1 x 108. The safety as well as the biological and the clinical effects of TP-DC were studied. Twenty seven pts were included. Ten of these pts had evaluable unresected tumor resistant to conventional chemotherapy. Results: TP-DC/CAT was well tolerated; the major adverse events being fever and skin erythema of low grade (grade 1 and grade 2). No grade 3 and 4 adverse events was noted. Two of 10 pts with evaluable unresected tumor achieved partial remission (6 months); 4 pts achieved stable disease (4 months). 13 of 16 pts receiving 1 x 108 DC developed a strong positive skin reaction to tumor lysates. In 6 pts, a positive skin reaction to tumor lysates was shown to be maintained in 12 months after the development of the positive skin reaction to tumor lysates. Conclusion: The results of this Phase I trial appear promising for further development in pts with advanced GI cancers. No significant financial relationships to disclose.