Open-label, multi-center, non-randomized, single-arm study to evaluate the safety and efficacy of dendritic cell immunotherapy in patients with refractory solid malignancies, on supportive care.
OBJECTIVE
A phase II clinical trial of an autologous dendritic cell (DC) formulation for the management of refractory solid malignant tumors was conducted across six sites in India with an objective to study safety and efficacy.


METHODS
A total of 51 patients with refractory cancer (either sex) with life expectancy ≥3 months, Eastern Cooperative Oncology Group score ≤2, available tumor tissue and adequate organ and bone marrow function were recruited. Monocytes obtained by leukapheresis, differentiated into DCs by cytokines and primed with autologous tumor lysate (fresh tissue biopsy or paraffin block). On the 8th day, mature DCs were analyzed for expression of CD40, CD80, CD83, CD86, DC205 and DC209. The treatment regime consisted of six doses (intravenous) over 14 weeks with 2 post-treatment follow-up visits, 6 weeks apart. Safety was assessed at all visits and responses were evaluated on days 58, 100 and 184 or at end of the study.


RESULTS
A total of 38 patients were evaluated for safety and efficacy. One adverse event classified as possibly related was an episode of rigors or chills with mild pyrexia during one infusion. Objective response rate by Response Evaluation Criteria In Solid Tumors was 28.9% (11/38) and immune-related response criteria was 42.1% (16/38); 90% confidence interval for objective response rate was (17.2, 43.3) and (28.5, 56.7) by Response Evaluation Criteria In Solid Tumors and immune-related response criteria, respectively. The median time to treatment progression was >9 weeks. Median overall survival was 397 days. An increase in the expression of interferon-γ was not significant.


CONCLUSIONS
Therapy was safe. The responses, time to treatment progression and survival are encouraging for patients with aggressive refractory disease.
Department of Oncology, Apollo Hospital, Bangalore, India.
Poonamalle Parthasarathy
PP
Bapsy
APAC Biotech Pvt Ltd, Gurgaon, India. Electronic address: drbandana@apacbiotech.com.
Bandana
B
Sharan
APAC Biotech Pvt Ltd, Gurgaon, India.
Chaitanya
C
Kumar
APAC Biotech Pvt Ltd, Gurgaon, India.
Rajeev Patrick
RP
Das
Narayan Hrudayalaya Hospital, Bangalore, India.
Bharath
B
Rangarajan
Ruby Hall Clinic, Pune, India.
Minish
M
Jain
Apollo Hospital, Hyderabad, India.
Venkata Sathya
VS
Suresh Attili
V.S. Hospital, Chennai, India.
Sundaram
S
Subramanian
Department of Medical Oncology, Sir Ganga Ram Hospital, New Delhi, India.
Shyam
S
Aggarwal
Nextvel Consulting LLP, Bangalore, India.
Mala
M
Srivastava
Department of Medical Oncology and Hematology, Medanta-the Medicity, Gurgaon, India.
Ashok
A
Vaid
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines; D002277:Carcinoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D002454:Cell Differentiation; D002457:Cell Extracts / Q000276:immunology; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007194:India; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D012008:Recurrence; D016019:Survival Analysis; D016896:Treatment Outcome
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D002457:Cell Extracts; D016207:Cytokines
cancer immunotherapy; dendritic cells; monocytes