June 26, 2022

Medical Trend

Medical News and Medical Resources

Targeting solid tumors: mRNA tumor vaccine combined with PD-(L)1 mAb

Targeting solid tumors: mRNA tumor vaccine combined with PD-(L)1 mAb



 

Targeting solid tumors: mRNA tumor vaccine combined with PD-(L)1 mAb

Due to the low response rate and drug resistance of patients, PD-(L)1 monoclonal antibody began to iterate technology on double antibody and polyclonal antibody on the one hand; Vaccines and other drugs have developed rapidly in recent years.

This article reviews the cooperation between BioNTech and Regeneron, Moderna and AstraZeneca, and explores the prospect of mRNA tumor vaccine combined with PD-(L)1 mAb in the field of solid tumors for readers.



BioNTech joins hands with Regeneron: Moderna joins hands with AstraZeneca

 

In recent years, with the rise of tumor immunotherapy, the exploration of the combination of mRNA tumor vaccine and PD-(L)1 monoclonal antibody for solid tumors has also become a research hotspot.

 

Targeting solid tumors: mRNA tumor vaccine combined with PD-(L)1 mAb

Slideshow from Moderna JPM2021

 

On March 8 , 2022 , BioNTech announced the expansion of its strategic cooperation with Regeneron to advance the combination program of the company’s blockbuster product BNT116 ( mRNA vaccine ) and Libtayo ( simiprilumab , PD-1 mAb ) , using Efficacy exploration in advanced non-small cell lung cancer.

 

The last cooperation between the two companies can be traced back to July 31 , 2020 , when the combined program of BNT111 ( mRNA vaccine ) and Libtayo was used in the research and exploration of melanoma.

This time, the cooperation is further expanded, and the layout is still in the field of non-small cell lung cancer with a high incidence in the world, which shows BioNTech ‘s confidence in the mRNA vaccine combined with immunotherapy developed by it.

 

Coincidentally, in addition to BioNTech , Modern , another leader in the field of mRNA research and development , has also begun to try to use its own IL-12 mRNA tumor vaccine ( MEDI1191 ) in combination with Durvalumab ( PD-L1 monoclonal antibody) in patients with advanced solid tumors.

 

In addition, Merck is cooperating with Moderna to develop tumor vaccines. The two parties are using Moderna vaccine in combination with Merck’s ace immune drug Keytruda in the research to explore the therapeutic effect in the field of advanced solid tumors.

 

It can be seen that the research plan of mRNA tumor vaccine combined with PD-(L) monoclonal antibody is rapidly advancing in clinical practice.

Next, we will take a detailed look at the currently disclosed efficacy data and mechanisms of action of different combination options.

 

 

BNT111

 

Targeting solid tumors: mRNA tumor vaccine combined with PD-(L)1 mAb
From BioNTech official website

 

BNT111 is BioNTech ‘s fastest-growing R&D pipeline and is indicated for advanced melanoma. BNT111 is an mRNA vaccine encoding 4 tumor – associated antigens ( tumor -associated antigens , TAAs ) including NY-ESO-1 , Tyrosinase , MAGE -A3 and TPTE . Injected into the patient’s body.

 

Targeting solid tumors: mRNA tumor vaccine combined with PD-(L)1 mAb

ImageFrom Sahin et al, Nature 2020

 


A dose-escalation phase 1 clinical trial (Lipo-MERIT trial, NCT02410733) enrolled a total of 56 patients, of which 30 patients received BNT111 alone and 26 patients received BNT111 in combination with PD-1 mAb.

 

Targeting solid tumors: mRNA tumor vaccine combined with PD-(L)1 mAb

From Sahin et al, Nature 2020

 

The combination group had 6 patients with CR , 2 with SD , and 9 with PD , which was better than the BNT111 monotherapy group. In addition, the data show that the BNT111 vaccine is safe. The most common side effects are mild to moderate fever and chills, which usually resolve within 24 hours of treatment.

 

Targeting solid tumors: mRNA tumor vaccine combined with PD-(L)1 mAbFrom Sahin et al, Nature 2020

 

As for why the combination group is significantly better than the single drug group, the researchers further used IFN – γ ELISpot technology to test the ability of CD4+ T cells and CD4+ T cells to recognize antigens in patients. The results showed that the T cells in the patient at least acquired the ability to specifically recognize at least one antigen among NY-ESO-1 , Tyrosinase , MAGE-A3 and TPTE after the vaccine infusion. Therefore, BNT111 combined with PD-1 monoclonal antibody can effectively activate immune cells.

 

 

 

MEDI1191

 

Phase I results of MEDI1191 (IL-12 mRNA cancer vaccine ) in combination with Durvalumab in advanced solid tumors were presented at ESMO TAT 2021 ( ESMO International Conference on Targeted Anti-Cancer Therapeutics).

 

From the 2021 ESMO TAT official website

 

 

Results showed that after intratumoral ( IT ) injection of MEDI1191 administered in combination with Durvalumab ( PD-L1 mAb) in 10 ( 6 immunotherapy-treated) patients with advanced solid tumors receiving one or more standard systemic therapies , there were two patients with immune response, the safety and tolerance were good, and no adverse reactions of grade ≥ 3 occurred. This initial result is very exciting , especially in patients who have failed immunotherapy. Can the specific mechanism be explained?

 

From Cancers 2021, 13, 167

 

 

First of all, let ’s start with IL-12 (interleukin- 12 ). IL-12 is produced by antigen-presenting cells and B cells. It is a pro- inflammatory cytokine in the form of a heterodimer. form secreted outside the cell. IL-12 plays an important role in immune regulation and can shape immune responses by directly inducing the development of T cell subsets and altering the function and fate of many cell populations that determine disease prognosis.

For example, by promoting the polarization of M1 macrophages and the production of IFN-γ by Th1 cells , the immune response against tumor cells is activated, thereby stimulating the production of CD8+ T and NK cells.


From Cancers 2021, 13, 167

 

 

In view of this, IL-12 can synergize with other treatment modalities to enhance the therapeutic effect. It has been used in the development of immunomodulators, CART technology, chemotherapy and radiotherapy, and vaccines.

 

From Moderna’s official website

 

Moderna ‘s tumor vaccine MEDI1191 is based on IL-12 . It is injected into the tumor, and the mRNA encoding the antigenic protein ( IL-12 ) is injected into the tumor, the mRNA enters the cell, the antigenic protein is translated, and the antigenic protein is presented on the cell surface. Secreted outside the cell to trigger an immune response.

 

 

 


Summary:

 

mRNA tumor vaccine and PD-(L)1 monoclonal antibody can be more targeted to tumor-associated antigens (TAAs) in mechanism, and play a role in synergistically activating effector T cells.

At present, preliminary explorations have been carried out in the clinical stage. In the future, it is hoped that more Exciting results with large sample sizes.

 

 

 

 

 

 

 

 


References:
[1] Nature. 2020 Sep;585(7823):107-112..
[2] Cancer Cell 36, 613–629, December 9, 2019 ª 2019 Elsevier Inc
[3] Cancers 2021, 13(2), 167; https://doi.org/10.3390/cancers13020167

Targeting solid tumors: mRNA tumor vaccine combined with PD-(L)1 mAb

(source:internet, reference only)


Disclaimer of medicaltrend.org