Local and systemic antitumor effects of activated autologous dendritic cells for intratumoral injection: A phase I/II trial.
Sub-category:
Vaccines
Category:
Developmental Therapeutics - Immunotherapy
Meeting:
2014 ASCO Annual Meeting
Abstract No:
TPS3133
Attend this session at the
2014 ASCO Annual Meeting!
Session: Developmental Therapeutics - Immunotherapy
Type: General Poster Session
Time: Sunday June 1, 8:00 AM to 11:45 AM
Location: S Hall A2
Personalize your Meeting experience with a suggested or customized itinerary!
Author(s): Vivek Subbiah, Ravi Murthy, Omar Kayaleh, Marnix Leo Bosch; The University of Texas MD Anderson Cancer Center, Houston, TX; M. D. Anderson Cancer Center, Orlando, Orlando, FL; Northwest Biotherapeutics Inc, Bethesda, MD
Abstract Disclosures
Abstract:
Background: Dendritic cells (DC) are antigen presenting cells proficient in inducing de novo immune responses, and the presence of intratumoral DCs confers a survival advantage to patients, likely due to an improved balance between the immune system and the growing tumor lesion. We have initiated a Phase I/II clinical trial to exploit this finding, by using partially activated autologous DCs (aDC; DCVax-Direct) for intratumoral injection in inoperable tumors for which limited treatment options exist. These aDC retain antigen uptake and presentation capability and are conditioned to complete the maturation process following injection, resulting in initiation of a broad anti-tumor immune response. Preclinical animal data have demonstrated that these aDC can mobilize both local and systemic immune responses, and effectively clear both injected (local) and non-injected (distal) inoperable tumor lesions. Methods: The Phase I component of the trial aims to enroll 6 patients each in following indications: colorectal cancer, lung cancer, breast cancer with brain metastases, pancreatic cancer, melanoma and ‘other’. Patients must have had at least one recent anti-tumor treatment other than active immune therapy prior to enrollment into the trial. A dose escalation across indications investigates the safety of 3 dose levels. The aDC are injected intratumorally, using imaging guidance, at days 0, 7 and 14, followed by injections at 8 and 16 weeks. Initial DLT assessments are done following the first three injections. Tumor biopsies are taken at the time of injections to assess local effects on the injection of aDC, and tumor response is assessed using both RECIST and Immune Related Response Criteria, starting 8 weeks after the first injection. The first dose cohort of the Phase I component has completed DLT assessments, and the second dose cohort’s enrollment is nearly complete. In addition, the “other” cohort of multiple cancers has been fully enrolled. Correlative immune-biomarkers studies to evaluate response and/or resistance mechanisms are planned. The Phase II component will enroll 24 patients in a selected indication, based on the results obtained in Phase I. Clinical trial information: NCT01882946.
AI
