Rationale for a novel immunotherapy of cancer with allogeneic lymphocyte infusion

Kondo, Masaru; McCarty, Mark F.

doi:10.1016/0306-9877(84)90017-3

Cited by 9 publications

(2 citation statements)

References 146 publications

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“…The use of transiently engrafting lymphocytes to stimulate antitumor immunity began in 1960 with the report of a patient with melanoma who achieved a disease response following infusion of lymphocytes from a second patients with melanoma who experienced spontaneous disease regression [79]. Several reports followed (reviewed in [80]), but without a detailed understanding of alloreactivity or significant mechanistic insights, interest in nonengrafting allogeneic cell therapy waned. The Fuchs group's interest in nonengrafting cell therapy was piqued by the observation of clinical responses of hematologic malignancies despite graft rejection after HaploSCT [81,82].…”

Section: Clinical Applicationsmentioning

confidence: 99%

Proceedings From the Fourth Haploidentical Stem Cell Transplantation Symposium (HAPLO2016), San Diego, California, December 1, 2016

Malki

Jones

et al. 2018

Biology of Blood and Marrow Transplantation

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The resurgence of haploidentical stem cell transplantation (HaploSCT) over the last decade is one of the most important advances in the field of hematopoietic stem cell transplantation (HSCT). The modified platforms of T cell depletion either ex vivo (CD34 cell selection, "megadoses" of purified CD34 cells, or selective depletion of T cells) or newer platforms of in vivo depletion of T cells, with either post-transplantation high-dose cyclophosphamide or intensified immune suppression, have contributed to better outcomes, with survival similar to that in HLA-matched donor transplantation. Further efforts are underway to control viral reactivation using modified T cells, improve immunologic reconstitution, and decrease the relapse rate post-transplantation using donor-derived cellular therapy products, such as genetically modified donor lymphocytes and natural killer cells. Improvements in treatment-related mortality have allowed the extension of haploidentical donor transplants to patients with hemoglobinopathies, such as thalassemia and sickle cell disease, and the possible development of platforms for immunotherapy in solid tumors. Moreover, combining HSCT from a related donor with solid organ transplantation could allow early tapering of immunosuppression in recipients of solid organ transplants and hopefully prevent organ rejection in this setting. This symposium summarizes some of the most important recent advances in HaploSCT and provides a glimpse in the future of fast growing field.

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Section: Clinical Applicationsmentioning

confidence: 99%

Proceedings From the Fourth Haploidentical Stem Cell Transplantation Symposium (HAPLO2016), San Diego, California, December 1, 2016

Malki

Jones

et al. 2018

Biology of Blood and Marrow Transplantation

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“…Since the 1960 s, several groups of investigators have tried to induce host antitumor immunity by adoptive cell transfer of allogeneic lymphocytes without utilizing hematopoietic stem cell transplantation (HSCT), and they called the favorable response elicited by this an "allogenic effect" [25][26][27]. In these studies, allogeneic mononuclear cells or lymphocytes were transferred into allogeneic hosts and induced some clinical benefits [28][29][30][31]. More recently, specialized allogeneic lymphocytes, namely mitomycin C-inactivated allogeneic lymphocytes, or effector/memory CD4 + T helper-1 (Th1) lymphocytes that were non-specifically activated by CD3/CD28 antibodies have been used [32][33][34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

Alloantigen-activated (AAA) CD4+ T cells reinvigorate host endogenous T cell immunity to eliminate pre-established tumors in mice

Mochizuki

Kobayashi

Takahashi

et al. 2021

J Exp Clin Cancer Res

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Background Cancer vaccines that induce endogenous antitumor immunity represent an ideal strategy to overcome intractable cancers. However, doing this against a pre-established cancer using autologous immune cells has proven to be challenging. “Allogeneic effects” refers to the induction of an endogenous immune response upon adoptive transfer of allogeneic lymphocytes without utilizing hematopoietic stem cell transplantation. While allogeneic lymphocytes have a potent ability to activate host immunity as a cell adjuvant, novel strategies that can activate endogenous antitumor activity in cancer patients remain an unmet need. In this study, we established a new method to destroy pre-developed tumors and confer potent antitumor immunity in mice using alloantigen-activated CD4+ (named AAA-CD4+) T cells. Methods AAA-CD4+ T cells were generated from CD4+ T cells isolated from BALB/c mice in cultures with dendritic cells (DCs) induced from C57BL/6 (B6) mice. In this culture, allogeneic CD4+ T cells that recognize and react to B6 mouse-derived alloantigens are preferentially activated. These AAA-CD4+ T cells were directly injected into the pre-established melanoma in B6 mice to assess their ability to elicit antitumor immunity in vivo. Results Upon intratumoral injection, these AAA-CD4+ T cells underwent a dramatic expansion in the tumor and secreted high levels of IFN-γ and IL-2. This was accompanied by markedly increased infiltration of host-derived CD8+ T cells, CD4+ T cells, natural killer (NK) cells, DCs, and type-1 like macrophages. Selective depletion of host CD8+ T cells, rather than NK cells, abrogated this therapeutic effect. Thus, intratumoral administration of AAA-CD4+ T cells results in a robust endogenous CD8+ T cell response that destroys pre-established melanoma. This locally induced antitumor immunity elicited systemic protection to eliminate tumors at distal sites, persisted over 6 months in vivo, and protected the animals from tumor re-challenge. Notably, the injected AAA-CD4+ T cells disappeared within 7 days and caused no adverse reactions. Conclusions Our findings indicate that AAA-CD4+ T cells reinvigorate endogenous cytotoxic T cells to eradicate pre-established melanoma and induce long-term protective antitumor immunity. This approach can be immediately applied to patients with advanced melanoma and may have broad implications in the treatment of other types of solid tumors.

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Regression of Melanoma Nodules in a Patient Treated With Ranitidine

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Rationale for a novel immunotherapy of cancer with allogeneic lymphocyte infusion

Cited by 9 publications

References 146 publications

Proceedings From the Fourth Haploidentical Stem Cell Transplantation Symposium (HAPLO2016), San Diego, California, December 1, 2016

Proceedings From the Fourth Haploidentical Stem Cell Transplantation Symposium (HAPLO2016), San Diego, California, December 1, 2016

Alloantigen-activated (AAA) CD4+ T cells reinvigorate host endogenous T cell immunity to eliminate pre-established tumors in mice

Regression of Melanoma Nodules in a Patient Treated With Ranitidine

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