Title |
Cytokines Produced by Dendritic Cells Administered Intratumorally Correlate with Clinical Outcome in Patients with Diverse Cancers
|
---|---|
Published in |
Clinical Cancer Research, August 2018
|
DOI | 10.1158/1078-0432.ccr-17-2707 |
Pubmed ID | |
Authors |
Vivek Subbiah, Ravi Murthy, David S. Hong, Robert M. Prins, Chitra Hosing, Kyle Hendricks, Deepthi Kolli, Lori Noffsinger, Robert Brown, Mary McGuire, Siquing Fu, Sarina Piha-Paul, Aung Naing, Anthony P. Conley, Robert S. Benjamin, Indreshpal Kaur, Marnix L. Bosch |
Abstract |
Purpose: Dendritic cells (DC) initiate adaptive immune responses through the uptake and presentation of antigenic material. In preclinical studies, intratumorally injected activated DCs (aDCs; DCVax-Direct) were superior to immature DCs in rejecting tumors from mice.Experimental Design: This single-arm, open-label phase I clinical trial evaluated the safety and efficacy of aDCs, administered intratumorally, in patients with solid tumors. Three dose levels (2 million, 6 million, and 15 million aDCs per injection) were tested using a standard 3 + 3 dose-escalation trial design. Feasibility, immunogenicity, changes to the tumor microenvironment after direct injection, and survival were evaluated. We also investigated cytokine production of aDCs prior to injection.Results: In total, 39 of the 40 enrolled patients were evaluable. The injections of aDCs were well tolerated with no dose-limiting toxicities. Increased lymphocyte infiltration was observed in 54% of assessed patients. Stable disease (SD; best response) at week 8 was associated with increased overall survival. Increased secretion of interleukin (IL)-8 and IL12p40 by aDCs was significantly associated with survival (P = 0.023 and 0.024, respectively). Increased TNFα levels correlated positively with SD at week 8 (P < 0.01).Conclusions: Intratumoral aDC injections were feasible and safe. Increased production of specific cytokines was correlated with SD and prolonged survival, demonstrating a link between the functional profile of aDCs prior to injection and patient outcomes. Clin Cancer Res; 1-12. ©2018 AACR. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 15 | 31% |
United Kingdom | 3 | 6% |
Hong Kong | 1 | 2% |
Argentina | 1 | 2% |
Australia | 1 | 2% |
Unknown | 27 | 56% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 46 | 96% |
Scientists | 2 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 56 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 7 | 13% |
Researcher | 6 | 11% |
Student > Bachelor | 6 | 11% |
Student > Doctoral Student | 4 | 7% |
Student > Master | 4 | 7% |
Other | 10 | 18% |
Unknown | 19 | 34% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 12 | 21% |
Immunology and Microbiology | 5 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 7% |
Biochemistry, Genetics and Molecular Biology | 3 | 5% |
Nursing and Health Professions | 2 | 4% |
Other | 7 | 13% |
Unknown | 23 | 41% |