Cellular Immunotherapy for Neuroblastoma: A Review of Current Vaccine and Adoptive T Cell Therapeutics

Louis, Chrystal U.; Brenner, Malcolm K.

doi:10.2174/138161209787315765

Cited by 16 publications

(17 citation statements)

References 50 publications

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“…Treatment with anti-GD2 MAbs is associated with significant side effects, including pain from reaction with GD2 antigens expressed on peripheral nerves and significant hypersensitivity reactions [31,32]. Investigators have therefore focused on ways to decrease the immunogenicity and the side effects of these MAbs (Table III).…”

Section: The Role Of Immunotherapy For Neuroblastomamentioning

confidence: 99%

“…Disease heterogeneity and down-regulation of MHC and co-stimulatory molecules by neuroblastoma tumors limit the effectiveness of any tumor-specific T cell immune response induced by a vaccine [32]. In order to increase the presentation of a wide range of TAAs and account for tumor heterogeneity, initial studies of vaccines for children with neuroblastoma employed cellular extracts or whole cell products, with some significant clinical responses seen [37–40].…”

Section: The Role Of Immunotherapy For Neuroblastomamentioning

confidence: 99%

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New aspects of neuroblastoma treatment: ASPHO 2011 symposium review

Zage

Louis

Cohn

2012

Pediatric Blood & Cancer

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Neuroblastoma is the most common extracranial solid tumor of childhood, and the outcomes for children with high‐risk and relapsed disease remain poor. However, new international strategies for risk stratification and for treatment based on novel tumor targets and including immunotherapy are being employed in attempts to improve the outcomes of children with neuroblastoma. A new international neuroblastoma risk classification system has been developed which is being incorporated into cooperative group clinical trials in North America, Japan, and Europe, resulting in standardized approaches for the initial evaluation and treatment stratification of neuroblastoma patients. Furthermore, novel treatment regimens are being developed based on improved understanding of neuroblastoma biology and on the recruitment of the immune system to specifically target neuroblastoma tumors. These approaches will lead to new therapeutic strategies that likely will improve the outcomes for children with neuroblastoma worldwide. Pediatr Blood Cancer 2012; 58: 1099–1105. © 2012 Wiley Periodicals, Inc.

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Section: The Role Of Immunotherapy For Neuroblastomamentioning

confidence: 99%

Section: The Role Of Immunotherapy For Neuroblastomamentioning

confidence: 99%

New aspects of neuroblastoma treatment: ASPHO 2011 symposium review

Zage

Louis

Cohn

2012

Pediatric Blood & Cancer

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“…Until recently, however, CAR-T cells had shown little evidence of antitumor activity against solid tumors and had only brief persistence in vivo. [5][6][7] It has been believed that engagement of the chimeric receptor by tumor antigens failed to provide the requisite costimulatory signals necessary for optimal expansion, function, and persistence because tumor cells, unlike professional antigen-presenting cells, lack costimulatory ligands and may express inhibitory ligands. Therefore, efforts have been made to incorporate the signaling endodomains of costimulatory molecules, such as CD28, OX40, and 41BB into CARs.…”

Section: Introductionmentioning

confidence: 99%

Antitumor activity and long-term fate of chimeric antigen receptor–positive T cells in patients with neuroblastoma

Louis

Savoldo

Dotti

et al. 2011

Blood

986

806

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We generated MHC-independent chimeric antigen receptors (CARs) directed to the GD2 antigen expressed by neuroblastoma tumor cells and treated patients with this disease. Two distinguishable forms of this CAR were expressed in EBV-specific cytotoxic T lymphocytes (EBV-CTLs) and activated T cells (ATCs). We have previously shown that EBV-CTLs expressing GD2-CARs (CAR-CTLs) circulated at higher levels than GD2-CAR ATCs (CAR-ATCs) early after infusion, but by 6 weeks, both subsets became low or undetectable. We now report the long-term clinical and immunologic consequences of infusions in 19 patients with high-risk neuroblastoma: 8 in remission at infusion and 11 with active disease. Three of 11 patients with active disease achieved complete remission, and persistence of either CAR-ATCs or CAR-CTLs beyond 6 weeks was associated with superior clinical outcome. We observed persistence for up to 192 weeks for CAR-ATCs and 96 weeks for CAR-CTLs, and duration of persistence was highly concordant with the percentage of CD4+ cells and central memory cells (CD45RO+CD62L+) in the infused product. In conclusion, GD2-CAR T cells can induce complete tumor responses in patients with active neuroblastoma; these CAR T cells may have extended, low-level persistence in patients, and such persistence was associated with longer survival. This study is registered at www.clinialtrials.gov as #NCT00085930.

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“…There have been some reviews already on this subject [8,30], the most recent one focusing specifically on neuroblastoma [31]. In 1999, Roskrow et al, reviewed primarily the preclinical studies that compared different adjuvants and immunogens in preparation for future clinical trials [30].…”

Section: Pediatric Cancer Vaccines: Current State-of-the-artmentioning

confidence: 99%

Cancer Vaccines: Emphasis on Pediatric Cancers

Guinipero¹,

Finn²

2010

CPD

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The success that vaccines have had in the fight with infectious diseases has not been mirrored in their use in the fight against cancer. The major differences are that cancer vaccines have been tested in the therapeutic rather than the prophylactic setting, and in older adults rather than in the pediatric population. Cancers, as well as current standard treatments, are highly immunosuppressive, which further compromises the success of therapeutic vaccines. Cancer is considered to be primarily a disease of the older age and yet many children suffer from or succumb to cancers such as leukemias, glioblastomas, neuroblastomas and sarcomas. Standard therapy, even when curative, is accompanied by serious side effects, including secondary tumors later in life. Due to the greater capacity of a young immune system to recover after cancer treatment, therapeutic vaccines are expected to have a better chance to elicit protective immunity and prevent cancer recurrence in children. In this review, we discuss the current efforts at designing and testing cancer vaccines in children with the focus on specific tumor antigens expressed by pediatric cancers.

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Cellular Immunotherapy for Neuroblastoma: A Review of Current Vaccine and Adoptive T Cell Therapeutics

Cited by 16 publications

References 50 publications

New aspects of neuroblastoma treatment: ASPHO 2011 symposium review

New aspects of neuroblastoma treatment: ASPHO 2011 symposium review

Antitumor activity and long-term fate of chimeric antigen receptor–positive T cells in patients with neuroblastoma

Cancer Vaccines: Emphasis on Pediatric Cancers

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