Tumor lysate-based vaccines: on the road to immunotherapy for gallbladder cancer

Rojas-Sepúlveda, Daniel; Tittarelli, Andrés; Gleisner, María Alejandra; Ávalos, Ignacio; Pereda, Carlos; Gallegos, Iván; González, Fermín E.; López, Mercedes; Butte, Jean M.; Roa, Juan Carlos; Fluxá, Paula; Salazar‐Onfray, Flavio

doi:10.1007/s00262-018-2157-5

Cited by 41 publications

(30 citation statements)

References 48 publications

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“…The protein concentration was estimated by Bradford's method using a biophotometer (Eppendorf). The human gallbladder cancer lysates (GBCa) (57), human ovarian cancer cell lysates from SKOV3 cell lines (ATCC) (OvCa), leukocyte lysed from PBMC and B16.F10 cell line lysate (B16 lysate) were lysed using the same method.…”

Section: Methodsmentioning

confidence: 99%

IRE1α Activation in Bone Marrow-Derived Dendritic Cells Modulates Innate Recognition of Melanoma Cells and Favors CD8+ T Cell Priming

et al. 2019

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The IRE1α/XBP1s signaling pathway is an arm of the unfolded protein response (UPR) that safeguards the fidelity of the cellular proteome during endoplasmic reticulum (ER) stress, and that has also emerged as a key regulator of dendritic cell (DC) homeostasis. However, in the context of DC activation, the regulation of the IRE1α/XBP1s axis is not fully understood. In this work, we report that cell lysates generated from melanoma cell lines markedly induce XBP1s and certain members of the UPR such as the chaperone BiP in bone marrow derived DCs (BMDCs). Activation of IRE1α endonuclease upon innate recognition of melanoma cell lysates was required for amplification of proinflammatory cytokine production and was necessary for efficient cross-presentation of melanoma-associated antigens without modulating the MHC-II antigen presentation machinery. Altogether, this work provides evidence indicating that ex-vivo activation of the IRE1α/XBP1 pathway in BMDCs enhances CD8+ T cell specific responses against tumor antigens.

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Section: Methodsmentioning

confidence: 99%

IRE1α Activation in Bone Marrow-Derived Dendritic Cells Modulates Innate Recognition of Melanoma Cells and Favors CD8+ T Cell Priming

et al. 2019

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“…These in vitro studies demonstrated that conditioned lysate-matured DCs strongly induced the activation of CD4 + and CD8 + T cells in both allogeneic and autologous cell co-cultures. Moreover, in vitro stimulated CD8 + T cells were able to recognize HLA-matched GBC cell lines, demonstrating efficient priming of DCs by cancer cells and a subsequent presentation of antigens to T cells [134]. These results opened the way for future immunotherapy approaches; however, other studies are needed to characterize immune infiltrates.…”

Section: Molecular Characteristics and Immune Infiltrates In Gbcmentioning

confidence: 89%

Molecular and Immunological Characterization of Biliary Tract Cancers: A Paradigm Shift Towards a Personalized Medicine

Malenica

Donadon

Lleo

2020

Cancers

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Biliary tract cancers (BTCs) are a group of rare cancers that account for up to 3–5% of cancer patients worldwide. BTCs include cholangiocarcinoma (CCA), gallbladder cancer (GBC), and ampulla of Vater cancer (AVC). They are frequently diagnosed at an advanced stage when the disease is often found disseminated. A late diagnosis highly compromises surgery, the only potentially curative option. Current treatment regimens include a combination of chemotherapeutic drugs gemcitabine with cisplatin that have a limited efficiency since more than 50% of patients relapse in the first year. More recently, an inhibitor of fibroblast growth factor receptor 2 (FGFR2) was approved as a second-line treatment, based on the promising results from the NCT02924376 clinical trial. However, novel secondary treatment options are urgently needed. Recent molecular characterization of CCA and GBC highlighted the molecular heterogeneity, etiology, and epidemiology in BTC development and lead to the classification of the extrahepatic CCA into four types: metabolic, proliferating, mesenchymal, and immune type. Differences in the immune infiltration and tumor microenvironment (TME) have been described as well, showing that only a small subset of BTCs could be classified as an immune “hot” and targeted with the immunotherapeutic drugs. This recent evidence has opened a way to new clinical trials for BTCs, and new drug approvals are highly expected by the medical community.

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“…Importantly, whole tumor lysates can be prepared in several ways, and the methods of inducing cell death, cell stress, or the chemical modification of proteins could impact the immunogenicity and efficacy of the therapy. Current immunogenic treatment modalities used for preconditioning tumor cell lysates include ultraviolet irradiation, oxidation-inducing modalities, and heat shock treatments [29, 32]. We previously showed that the heat shock treatment induces the release of well-established DAMPs, such as CRT and HMGB1, as well as putative DAMPs, such as haptoglobin.…”

Section: Discussionmentioning

confidence: 99%

“…The use of allogeneic heat shock-conditioned tumor cell lysates provides a vast number of different tumor-associated antigens described for melanoma and also delivers different damage-associated molecular patterns (DAMPs) induced by the heat shock, such as high mobility group box-1 (HMGB1) and plasma membrane translocated calreticulin (CRT) necessary for the proper maturation, activation, and cross-presentation of tumor-associated antigens by DCs, enhancing their antitumor-induced responses [28–30]. Recently, we have extended our results to other types of tumors, such as prostate cancer and gallbladder cancer, using specific allogeneic heat shock-conditioned cell lysates for each tumor [31, 32].…”

Section: Introductionmentioning

confidence: 99%

Dendritic Cells Loaded with Heat Shock-Conditioned Ovarian Epithelial Carcinoma Cell Lysates Elicit T Cell-Dependent Antitumor Immune Responses In Vitro

Flores

Hevia

Tittarelli

et al. 2019

Journal of Immunology Research

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Ovarian epithelial carcinoma (OEC) is the most frequent ovarian tumor, characterized by a high mortality in advanced stages where conventional therapies are not effective. Based on the role of the immune system in the progression of this disease, immunotherapy using checkpoint blockade has been considered as a therapeutic alternative. Nevertheless, its results do not match up to the positive results in entities like melanoma and other malignancies, suggesting the need to find other therapies to be used alone or in combination. Dendritic cell- (DC-) based vaccines have shown promising results in several types of cancer, such as melanoma, prostate, and lung cancers, due to the essential role played by DCs in the activation of specific T cells, thus using other ways of activating the immune response than immune checkpoint blockade. During the last decade, we have used DC-based vaccines loaded with an allogeneic heat shock-conditioned melanoma cell lysate in the treatment of advanced stage patients in a series of clinical trials. In these studies, 60% of treated patients showed immunological responses which correlated positively with improved survival. Considering the relevance of ovarian cancer and the promising results of our DC-based vaccine, we show here that heat shock-conditioned cell lysates derived from ovarian epithelial carcinoma cell lines have the potential to induce the phenotypic and functional maturation of human DC, which in turn, is able to induce an efficient CD4+ and CD8+ T cell-mediated immune responses against ovarian cancer cell lines in vitro. In summary, OEC heat shock-conditioned cell lysate-loaded DCs may be considered for future combined immunotherapy approaches against ovarian tumors.

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Tumor lysate-based vaccines: on the road to immunotherapy for gallbladder cancer

Cited by 41 publications

References 48 publications

IRE1α Activation in Bone Marrow-Derived Dendritic Cells Modulates Innate Recognition of Melanoma Cells and Favors CD8+ T Cell Priming

IRE1α Activation in Bone Marrow-Derived Dendritic Cells Modulates Innate Recognition of Melanoma Cells and Favors CD8+ T Cell Priming

Molecular and Immunological Characterization of Biliary Tract Cancers: A Paradigm Shift Towards a Personalized Medicine

Dendritic Cells Loaded with Heat Shock-Conditioned Ovarian Epithelial Carcinoma Cell Lysates Elicit T Cell-Dependent Antitumor Immune Responses In Vitro

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