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Diffuse Intrinsic Pontine Glioma
Published in David A. Walker, Giorgio Perilongo, Roger E. Taylor, Ian F. Pollack, Brain and Spinal Tumors of Childhood, 2020
Katherine E. Warren, Carolyn R. Freeman, Dannis G. van Vuurden
An alternate immunotherapy approach being evaluated in children with DIPG is vaccine therapy, intended to elicit an immune response to antigens overexpressed by tumor cells.104 In a pilot study, vaccine developed to target the glioma-associated antigens EphA2, interleukin-13 receptor alpha 2, and survivin, was administered subcutaneously every 3 weeks for eight courses to children with brainstem glioma treated with radiation therapy (n = 14) and children with newly diagnosed brainstem or high-grade glioma who were treated with radiation and concurrent chemotherapy (n = 12). Twenty-one of the 26 patients enrolled had evidence of an immune response by enzyme-linked immunosorbent spot analysis. Notably, five children with brainstem glioma developed symptomatic pseudoprogression which was severe in some cases, but responded to dexamethasone treatment and was associated with longer survival. It is important to note that patients enrolled for this initial safety and feasibility study were a select group in that patients were required to be HLA-A2-positive and be on no more than 0.1 mg/kg (maximum 4 mg) dexamethasone per day. This approach remains under active investigation.
Tyrosine Kinase Inhibitors: Targets Other Than FLT3, BCR-ABL, and c-KIT
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Suzanne R. Hayman, Judith E. Karp
The antigenicities of these target molecules may form the basis for immunomodulatory approaches, including vaccines. The rationale behind the development of vaccines directed against Hsps are the observations that Hsp90 and Hsp70 are expressed on the surface of certain tumor cells and are readily accessible to the host immune system. Hsps themselves may be antigenic, but recent data suggest that Hsp-peptide complexes may be what actually evoke the immune response (2). Indirect support of this includes the lack of autoimmunity observed to date, which has been attributed to the immune response probably targeting a Hsp-peptide complex rather than the carrier Hsp. In contrast to the vaccines being evaluated for Hsps, those being developed against VEGFR-2/ KDR target an auto-antigen associated with angiogenesis rather than tumor cells. A variety of vaccine constructs including dendritic cells pulsed with soluble VEGFR-2 and xenogeneic ECs have been used in an attempt to breach immune tolerance and, at the same time, decrease angiogenesis and associated tumor growth at least in part through induction of immune reactivity (91,92). The development of adjuvant vaccine therapy remains a promising area of investigation.
Lung Cancer Vaccines
Published in Kishan J. Pandya, Julie R. Brahmer, Manuel Hidalgo, Lung Cancer, 2016
Cheryl Ho, Oliver Gautschi, Primo N. Lara, David R. Gandara, Angela M. Davies
A second trial with the same autologous GVAX platform was performed by Nemunaitis et al. (48). Two cohorts of patients were enrolled: an early stage cohort (cohort A) with stage IB/II NSCLC and an advanced stage cohort (cohort B) with previously treated stage III and IV disease. Intradermal injections of vaccine were administered every two weeks for three to six vaccinations. Eighty-three patients had tumor harvested and 43 initiated vaccine therapy (cohort A, 10 and cohort B, 33). With a median follow-up of 20 months, 6 patients in cohort A have had recurrence. Among the patients who received vaccination in cohort B, the median progression-free survival was four months and the median overall survival, 12 months. Of interest, two patients with BAC in the advanced-stage cohort achieved a complete response. It has been hypothesized that this unique histological subtype of NSCLC may be more amenable to immunologic therapy than other variants of NSCLC because of a possible retroviral etiology with parallels being drawn between BAC and a retroviral-associated pulmonary disease in sheep—Jaagsietke (72,73). Based on the promise of this approach, the Southwest Oncology Group (S0310) has conducted a phase II trial of GVAX (CG8123) in patients with advanced BAC. This trial has just completed accrual and the results are anticipated in 2007.
Intranodal Administration of Neoantigen Peptide-loaded Dendritic Cell Vaccine Elicits Epitope-specific T Cell Responses and Clinical Effects in a Patient with Chemorefractory Ovarian Cancer with Malignant Ascites
Published in Immunological Investigations, 2021
Takashi Morisaki, Tetsuro Hikichi, Hideya Onishi, Takafumi Morisaki, Makoto Kubo, Tatsuya Hirano, Sachiko Yoshimura, Kazuma Kiyotani, Yusuke Nakamura
These results collectively indicate that MHC class-I-restricted neoantigen peptide-loaded DC vaccine could induce tumor-specific responses with an increase in the neoantigen-specific T cells in the peripheral blood and tumor site. However, we recognize the limitations of a single patient study, and further studies are needed to assess and monitor the anti-tumor effect of vaccine therapy. Nevertheless, the clinical and immunological effects in the patient with an even lower mutational burden will be meaningful, considering that neoantigen-targeting immunotherapy is an alternative approach to immune checkpoint inhibitors, and thus might be a promising therapy for chemorefractory cancer. Moreover, immunotherapy that targets neoantigens, such as neoantigen-peptide-loaded DC vaccines, are tumor-specific with minimal off-target effects, and are thus considered to be safe (Kissick 2018).
Improving long-term survival in diffuse intrinsic pontine glioma
Published in Expert Review of Neurotherapeutics, 2020
James Felker, Alberto Broniscer
A separate approach to augment the anti-tumor immune response is the use of vaccine therapy. The rationale for this therapy is to induce a cytotoxic T-cell response by introducing an antigen (protein or DNA/RNA) to induce an immune response, thereby tipping the scales of the immune microenvironment to immunostimulatory. Peptide vaccines containing the antigens of EphA2, IL-13Ra2, and survivin demonstrated some clinical response, including PsP in pilot studies [115,116]. Additionally, a peptide vaccine taking advantage of the recurrent mutant histone protein H3 K27 M by targeting the mutant histone directly has been successful in pre-clinical studies [117]. Again, this approach will be limited by the cold immune environment in DIPG as well as the fact that these vaccines will only induce an immune response in patients with specific HLA types (in this case A2). Another vaccine approach is the use of autologous dendritic cell vaccine (ADCV) [118]. ADCVs are made by leukapheresis of monocytic cells from patients, exposing them with tumor-cell antigens, and then giving them back as a vaccine [119]. A trial evaluating this is ongoing (NCT03396575).
Combination treatment of advanced pancreatic cancer using novel vaccine and traditional therapies
Published in Expert Review of Anticancer Therapy, 2018
Hiroto Matsui, Shoichi Hazama, Yoshitaro Shindo, Hiroaki Nagano
Immunotherapy is considered promising as a fourth-line treatment against solid cancers following surgery, chemotherapy, and radiation therapy. Although the effect of immunotherapy including cancer vaccine therapy is modest compared to other therapies such as chemotherapy, it has few adverse events and is characterized by a sustained specific therapeutic effect due to immunologic memory. In recent years, the emergence of immune-checkpoint blockade has increased the expectation for immunotherapy against solid cancers including pancreatic cancer. However, in a clinical trial of immunotherapy alone against pancreatic cancer, efficacy was confirmed in some subgroups, but the overall prognosis was not improved. It was also reported that high tumor mutation burden (TMB) correlates with the effects of immune-checkpoint blockade and other immunotherapies [4,5]. On the other hand, pancreatic cancer has a low TMB, so it may be difficult to expect that immunotherapy alone would have effects against pancreatic cancer. Therefore, it is necessary to use a combination of traditional chemotherapies whose effects have been proven, as well as new immunotherapies including cancer vaccines.