Cancer Stem Cell Treatment

Autologous Dendritic Cell Therapy for Cancer is available at SIRM

Cancer represents one of the major causes of mortality worldwide. More than half of patients suffering from cancer succumb to their condition. The primary approaches to treating cancer are surgical resection followed by radiation therapy and chemotherapy. These treatments have resulted in significant benefits to patients with the majority of tumor types, and the clinical outcomes have become more satisfactory. It is recognized that multidisciplinary treatments should be used in cancer treatments, another option proposed for this is immunotherapy. The combination of the traditional methods of surgery, chemotherapy and radiotherapy with immunotherapy, is a new way for anti-cancer therapies to reduce the mortality of cancer patients. The dysfunction of the antigen-specific T cells required to kill the cancer leads to cancer cells being able to grow in cancer patients. Active and adoptive T cell immunotherapies generate T cells that can target cancer cells.

Dendritic cells (DCs) are immune cells that function as antigen-presenting cells. They are able to activate naive CD4+ T helper cells and unprimed CD8+ cytotoxic T lymphocytes. Active immunotherapy, represented by DC-based regimens, has been used to produce tumor-specific antigen-presenting cells and to generate cytotoxic T lymphocyte responses against cancer cells. DCs can capture antigens, process them, and present them with co-stimulation cytokines/messengers to initiate an immune response, like inducing primary T-cell responses.

Adoptive immunotherapy, as conducted at our Asian Stem Cell Institute, is a personalized therapy that uses a patient’s own anti-tumor immune cells to kill cancer cells and may be used to treat several types of cancer, and represents another therapeutic approach against cancer. To date, the adoptive immunotherapy approach is one of the most effective methods for using the body’s immune system to treat cancer. To be used clinically, protocols for the development of these functional DCs must be established for in-clinic use via defined, xenobiotic-free medium conditions.

The purpose of the present study is to determine the cellular immune response in terms of the delayed-type hyper-sensitivity (DTH) skin test and evaluate the subjective clinical outcome and safety of the regimen in cancer patients receiving a DC vaccine.

Vaccination against a single antigen is available using purified and synthetic products, but these have disadvantages because it is unknown which of the identified antigens have the potential to induce an effective antitumor immune response. This study uses unfractionated, autologous, tumor-derived antigens in the form oftumor cell lysates which circumvents this disadvantage.

Tumor lysates as addressed in this protocol, contain multiple known as well as unknown antigens that can be presented to T cells by both MHC class I- and class II-pathways. Therefore, lysate-loaded DCs are more likely to induce the more preferred polyclonal expansion of T cells, including MHC class II restricted T-helper cells. These have been recognized to play an important role in the activation of Cytotoxic T Lymphocytes (CTLs), probably the most important cells in effecting an antitumor immune response. The generation of CTL clones with multiple specificities may be an advantage in heterogeneous tumors and could also reduce the risk of tumor escape variants. Furthermore, lysate from the autologous tumor can be used independently of the HLA type of the patient. A drawback of unfractionated tumor antigens is the possibility of inducing an autoimmune reactivity to epitopes that are shared by normal tissues. However, in clinical trials using lysate or whole tumor cells as the source of antigen, no clinically relevant autoimmune responses have ever been detected.

Personalized dendritic cell vaccines for cancer, via adoptive immunotherapy, are successfully developed and autologously administered to patients coming to Asia, and more specifically, within the Philippines at the Subic Institute for Regenerative Medicine. The results of this case study of cancer and immunotherapy via pulsed dendritic cells, can serve as another example of safety for future cancer vaccine development.

Dendritic Cell Therapy for Cancer:
Related Articles Characterization of an Immunogenic Mutation in a Patient with Metastatic Triple-Negative Breast Cancer. Clin Cancer Res. 2017 Aug 01;23(15):4347-4353 Authors: Assadipour Y, Zacharakis N, Crystal JS, Prickett TD, Gartner JJ, Somerville RPT, Xu H, Black MA, Jia L, Chinnasamy H, Kriley I, Lu L, Wunderlich JR, Zheng Z, Lu YC, Robbins PF, Rosenberg SA, Goff SL, Feldman SA Abstract Purpose: The administration of autologous tumor-infiltrating lymphocytes (TILs) can mediate durable tumor regressions in patients with melanoma likely based on the recognition of immunogenic somatic mutations expressed by the cancer. There are limited data regarding the immunogenicity of mutations in breast cancer. We sought to identify immunogenic nonsynonymous mutations in a patient with triple-negative breast cancer (TNBC) to identify and isolate mutation-reactive TILs for possible use in adoptive cell transfer.Experimental Design: A TNBC metastasis was resected for TIL generation and whole-exome sequencing. Tandem minigenes or long 25-mer peptides encoding selected mutations were electroporated or pulsed onto autologous antigen-presenting cells, and reactivity of TIL was screened by upregulation of CD137 and IFNγ ELISPOT. The nature of the T-cell response against a unique nonsynonymous mutation was characterized.Results: We identified 72 nonsynonymous mutations from the tumor of a patient with TNBC. CD4+ and HLA-DRB1*1501-restricted TILs isolated from this tumor recognized a single mutation in RBPJ (recombination signal binding protein for immunoglobulin kappa J region). Analysis of 16 metastatic sites revealed that the mutation was ubiquitously present in all samples.Conclusions: Breast cancers can express naturally processed and presented unique nonsynonymous mutations that are recognized by a patient's immune system. TILs recognizing these immunogenic mutations can be isolated from a patient's tumor, suggesting that adoptive cell transfer of mutation-reactive TILs could be a viable treatment option for patients with breast cancer. Clin Cancer Res; 23(15); 4347-53. ©2017 AACR. PMID: 28377481 [PubMed - indexed for MEDLINE]
Read more...

Quick Contact Form