SCYNAPSIS
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Image credit by Cancer Treatment Centers of America
Image credit by Cancer Treatment Centers of America
Image credit by Cancer Treatment Centers of America
Pablo Avalos Prado
Pablo Avalos Prado
Pablo Avalos Prado
Neuroscientist & Medical Writer
Neuroscientist & Medical Writer
Neuroscientist & Medical Writer
May 15, 2023
May 15, 2023
May 15, 2023
Promising preliminary results for pancreatic cancer treatment with BioNTech mRNA vaccine
Promising preliminary results for pancreatic cancer treatment with BioNTech mRNA vaccine
Promising preliminary results for pancreatic cancer treatment with BioNTech mRNA vaccine
A phase I clinical trial has reported specific immune response and delayed recurrence in patients with surgically resected pancreatic ductal adenocarcinoma following individualized messenger RNA (mRNA)-based treatment developed by BioNTech and Roche.
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death worldwide, with a survival rate of 12% whose only curative treatment is surgery. A major problem of PDAC tumors is that they do not express many specific neoantigens, mutation-generated proteins absent from healthy tissues that mark cancers as foreign to immune cells.
Over the last years, mRNA-based vaccines have become a promising - if not first line - therapy in the field of cancer and immunology, as evidenced by the Covid-19 pandemics, because they facilitate both rapid and customized delivery of neoantigens. In this regard, BioNTech and Roche have teamed up to develop a mRNA vaccine that has been tested on 16 patients with surgically resected PDAC in a phase I clinical trial (ID: NCT04161755).
A personalized mRNA vaccine that triggers long-lasting immune response
To provide an individualized treatment, the DNA of resected tumors of patients enrolled in the study was sequenced to predict and select neoantigens that could be integrated in the mRNA vaccine. Following a dose of the adjuvant atezolizumab (a compound that boosts antigenic response), the patients underwent an 8 days treatment with daily injections of cevumeran, the vaccine that delivers the mRNA that is uptaken by the “antigen-presenting cells'' of the body. Antigen-presenting cells generate and bind these neoantigenic markers that will be recognized by T-cells, the activators of the immune response. After having this treatment, patients received 12 cycles of chemotherapy (with mFOLFIRINOX) and were followed up up to 2 years.
The study, published last week in Nature, shows that half of the patients generated high-magnitude T-cell responses to the vaccine that were quantified by the detection of cytokines, immune molecules that are released when T-cells are stimulated. In addition, cevumeran administration only induced mild adverse effects in all patients, showing the safe profile of this treatment shortly after tumor surgery and its ability to induce immune response in a large proportion of patients with PDAC. Moreover, T-cell activation persisted up to 2 years despite post-vaccination chemotherapy, indicating the durability of this new treatment.
Perspectives and future prospect for mRNA-based vaccines against PDAC
The authors of this work correlated the delayed recurrence of PDAC observed in the participants with the long-lasting immune response triggered by the mRNA-vaccine combined with adjuvant and chemotherapy, a promising result to be validated in an imminent follow-up global randomized trial (IMCODE 003, BNT122).
However, the authors highlight the need for biomarkers to select optimal patients and tumors for this treatment since 50 % of patients did not show immune response to the vaccine. For this, they propose to optimize the mRNA vaccine potency and to explore more tumoral areas that could help to discover more genetic aberrations. Finally, they also suggest that this treatment should be considered for patients who are not in late stages of disease, since most mRNA-based vaccines show a preventive and not a therapeutic profile.
In light of these promising preliminary results, further research holds great potential for enhancing the efficacy of mRNA vaccines in pancreatic cancer treatment and expanding the benefits to a wider range of patients.
Original article
A phase I clinical trial has reported specific immune response and delayed recurrence in patients with surgically resected pancreatic ductal adenocarcinoma following individualized messenger RNA (mRNA)-based treatment developed by BioNTech and Roche.
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death worldwide, with a survival rate of 12% whose only curative treatment is surgery. A major problem of PDAC tumors is that they do not express many specific neoantigens, mutation-generated proteins absent from healthy tissues that mark cancers as foreign to immune cells.
Over the last years, mRNA-based vaccines have become a promising - if not first line - therapy in the field of cancer and immunology, as evidenced by the Covid-19 pandemics, because they facilitate both rapid and customized delivery of neoantigens. In this regard, BioNTech and Roche have teamed up to develop a mRNA vaccine that has been tested on 16 patients with surgically resected PDAC in a phase I clinical trial (ID: NCT04161755).
A personalized mRNA vaccine that triggers long-lasting immune response
To provide an individualized treatment, the DNA of resected tumors of patients enrolled in the study was sequenced to predict and select neoantigens that could be integrated in the mRNA vaccine. Following a dose of the adjuvant atezolizumab (a compound that boosts antigenic response), the patients underwent an 8 days treatment with daily injections of cevumeran, the vaccine that delivers the mRNA that is uptaken by the “antigen-presenting cells'' of the body. Antigen-presenting cells generate and bind these neoantigenic markers that will be recognized by T-cells, the activators of the immune response. After having this treatment, patients received 12 cycles of chemotherapy (with mFOLFIRINOX) and were followed up up to 2 years.
The study, published last week in Nature, shows that half of the patients generated high-magnitude T-cell responses to the vaccine that were quantified by the detection of cytokines, immune molecules that are released when T-cells are stimulated. In addition, cevumeran administration only induced mild adverse effects in all patients, showing the safe profile of this treatment shortly after tumor surgery and its ability to induce immune response in a large proportion of patients with PDAC. Moreover, T-cell activation persisted up to 2 years despite post-vaccination chemotherapy, indicating the durability of this new treatment.
Perspectives and future prospect for mRNA-based vaccines against PDAC
The authors of this work correlated the delayed recurrence of PDAC observed in the participants with the long-lasting immune response triggered by the mRNA-vaccine combined with adjuvant and chemotherapy, a promising result to be validated in an imminent follow-up global randomized trial (IMCODE 003, BNT122).
However, the authors highlight the need for biomarkers to select optimal patients and tumors for this treatment since 50 % of patients did not show immune response to the vaccine. For this, they propose to optimize the mRNA vaccine potency and to explore more tumoral areas that could help to discover more genetic aberrations. Finally, they also suggest that this treatment should be considered for patients who are not in late stages of disease, since most mRNA-based vaccines show a preventive and not a therapeutic profile.
In light of these promising preliminary results, further research holds great potential for enhancing the efficacy of mRNA vaccines in pancreatic cancer treatment and expanding the benefits to a wider range of patients.
Original article
A phase I clinical trial has reported specific immune response and delayed recurrence in patients with surgically resected pancreatic ductal adenocarcinoma following individualized messenger RNA (mRNA)-based treatment developed by BioNTech and Roche.
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death worldwide, with a survival rate of 12% whose only curative treatment is surgery. A major problem of PDAC tumors is that they do not express many specific neoantigens, mutation-generated proteins absent from healthy tissues that mark cancers as foreign to immune cells.
Over the last years, mRNA-based vaccines have become a promising - if not first line - therapy in the field of cancer and immunology, as evidenced by the Covid-19 pandemics, because they facilitate both rapid and customized delivery of neoantigens. In this regard, BioNTech and Roche have teamed up to develop a mRNA vaccine that has been tested on 16 patients with surgically resected PDAC in a phase I clinical trial (ID: NCT04161755).
A personalized mRNA vaccine that triggers long-lasting immune response
To provide an individualized treatment, the DNA of resected tumors of patients enrolled in the study was sequenced to predict and select neoantigens that could be integrated in the mRNA vaccine. Following a dose of the adjuvant atezolizumab (a compound that boosts antigenic response), the patients underwent an 8 days treatment with daily injections of cevumeran, the vaccine that delivers the mRNA that is uptaken by the “antigen-presenting cells'' of the body. Antigen-presenting cells generate and bind these neoantigenic markers that will be recognized by T-cells, the activators of the immune response. After having this treatment, patients received 12 cycles of chemotherapy (with mFOLFIRINOX) and were followed up up to 2 years.
The study, published last week in Nature, shows that half of the patients generated high-magnitude T-cell responses to the vaccine that were quantified by the detection of cytokines, immune molecules that are released when T-cells are stimulated. In addition, cevumeran administration only induced mild adverse effects in all patients, showing the safe profile of this treatment shortly after tumor surgery and its ability to induce immune response in a large proportion of patients with PDAC. Moreover, T-cell activation persisted up to 2 years despite post-vaccination chemotherapy, indicating the durability of this new treatment.
Perspectives and future prospect for mRNA-based vaccines against PDAC
The authors of this work correlated the delayed recurrence of PDAC observed in the participants with the long-lasting immune response triggered by the mRNA-vaccine combined with adjuvant and chemotherapy, a promising result to be validated in an imminent follow-up global randomized trial (IMCODE 003, BNT122).
However, the authors highlight the need for biomarkers to select optimal patients and tumors for this treatment since 50 % of patients did not show immune response to the vaccine. For this, they propose to optimize the mRNA vaccine potency and to explore more tumoral areas that could help to discover more genetic aberrations. Finally, they also suggest that this treatment should be considered for patients who are not in late stages of disease, since most mRNA-based vaccines show a preventive and not a therapeutic profile.
In light of these promising preliminary results, further research holds great potential for enhancing the efficacy of mRNA vaccines in pancreatic cancer treatment and expanding the benefits to a wider range of patients.
Original article