Results of a phase I study utilizing monocyte‐derived dendritic cells pulsed with tumor RNA in children with stage 4 neuroblastoma

Caruso, Denise; Orme, Lisa; Amor, Gerlinda M.; Neale, Alana M.; Radcliff, Fiona J.; Downie, Peter; Tang, Mimi L.K.; Ashley, David M.

doi:10.1002/cncr.20911

Cited by 98 publications

(47 citation statements)

References 27 publications

(28 reference statements)

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“…14,26 Further, some trials have made use of immature DCs. 18,[27][28][29] Interestingly, responses to unloaded matured DCs were recently published in a lung cancer DC vaccine trial. 34 The mockDC-response in our melanoma trial may represent an autologous mixed lymphocyte reaction (AMLR).…”

Section: Discussionmentioning

confidence: 99%

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Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA

et al. 2006

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We have developed an individualized melanoma vaccine based on transfection of autologous dendritic cells (DCs) with autologous tumor-mRNA. Dendritic cells loaded with complete tumor-mRNA may generate an immune response against a broad repertoire of antigens, including unique patient-specific antigens. The purpose of the present phase I/II trial was to evaluate the feasibility and safety of the vaccine, and the ability of the DCs to elicit T-cell responses in melanoma patients. Further, we compared intradermal (i.d.) and intranodal (i.n.) vaccine administration. Twenty-two patients with advanced malignant melanoma were included, each receiving four weekly vaccines. Monocyte-derived DCs were transfected with tumor-mRNA by electroporation, matured and cryopreserved. We obtained successful vaccine production for all patients elected. No serious adverse effects were observed. A vaccine-specific immune response was demonstrated in 9/19 patients evaluable by T-cell assays (T-cell proliferation/interferon-g ELISPOT) and in 8/18 patients evaluable by delayed-type hypersensitivity (DTH) reaction. The response was demonstrated in 7/10 patients vaccinated intradermally and in 3/12 patients vaccinated intranodally. We conclude that immuno-gene-therapy with the described DC-vaccine is feasible and safe, and that the vaccine can elicit in vivo T-cell responses against antigens encoded by the transfected tumor-mRNA. The response rates do not suggest an advantage in applying i.n. vaccination. Cancer Gene Therapy (2006) 13, 905-918.

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Section: Discussionmentioning

confidence: 99%

“…To date have been reported a pilot vaccination of a patient with lung cancer 26 followed by three phase I trials, in renal cancer, 27 pediatric brain cancer 28 and neuroblastoma. 29 The phase I studies all applied vaccination with immature DCs that were transfected by simple coincubation with tumor-RNA.…”

Section: Introductionmentioning

confidence: 99%

Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA

et al. 2006

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“…34 Furthermore, some studies only include cytotoxity assays that may not reveal an AMLR. 35 Finally, several early trials made use of immature DCs, [36][37][38] while DC maturation is considered to be important for the initiation of AMLR.…”

Section: Discussionmentioning

confidence: 99%

Immune response and long-term clinical outcome in advanced melanoma patients vaccinated with tumor-mRNA-transfected dendritic cells

et al. 2016

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The most effective anticancer immune responses are probably directed against patient-specific neoantigens. We have developed a melanoma vaccine targeting this individual mutanome based on dendritic cells (DCs) loaded with autologous tumor-mRNA. Here, we report a phase I/II trial evaluating toxicity, immune response and clinical outcome in 31 metastatic melanoma patients. The first cohort (n D 22) received the vaccine without any adjuvant; the next cohort (n D 9) received adjuvant IL2. Each subject received four weekly intranodal or intradermal injections, followed by optional monthly vaccines. Immune response was evaluated by delayed-type hypersensitivity (DTH), T cell proliferation and cytokine assays. Data were collected for 10 y after inclusion of the last patient. No serious adverse events were detected. In the intention-to-treat-cohort, we demonstrated significantly superior survival compared to matched controls from a benchmark meta-analysis (1 y survival 43% vs. 24%, 2 y 23% vs. 6.6%). A tumorspecific immune response was demonstrated in 16/31 patients. The response rate was higher after intradermal than intranodal vaccination (80% vs. 38%). Immune responders had improved survival compared to non-responders (median 14 mo vs. 6 mo; p D 0.030), and all eight patients surviving >20 mo were immune responders. In addition to the tumor-specific response, most patients developed a response against autologous DC antigens. The cytokine profile was polyfunctional and did not follow a Th1/Th2 dichotomy. We conclude that the favorable safety profile and evidence of a possible survival benefit warrant further studies of the RNA/DC vaccine. The vaccine appears insufficient as monotherapy, but there is a strong rationale for combination with checkpoint modulators.

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“…One of these patients remained alive with stable disease 14 mo after diagnosis. 72 Cancer Testis Antigens (CTAs) are a group of antigens expressed on many tumor types including pediatric sarcomas and neuroblastoma. CTAs comprise 70 families with over 140 antigens.…”

Section: Dendritic Cell Based Vaccinesmentioning

confidence: 99%

Targeted immunotherapy for pediatric solid tumors

Kopp

Katsanis

2015

OncoImmunology

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Results of a phase I study utilizing monocyte‐derived dendritic cells pulsed with tumor RNA in children with stage 4 neuroblastoma

Abstract: DC(RNA) vaccines were both safe and feasible in children with Stage 4 neuroblastoma. Humoral responses to tumor were detected, although remained immunosuppressed at the time of administration, limiting efficacy.

Cited by 98 publications

References 27 publications

Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA

Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA

Immune response and long-term clinical outcome in advanced melanoma patients vaccinated with tumor-mRNA-transfected dendritic cells

Targeted immunotherapy for pediatric solid tumors

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