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Enhancing host immune responses against solid tumors
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Get them answered by the team at Daiichi Sankyo.
Background

Most solid tumors are heterogeneous and have an immunosuppressive tumor microenvironment (TME). These characteristics could be the reason why the therapeutic efficacy of T cell engagers (TCE) and chimeric antigen receptor (CAR)-T cell therapies in solid tumors is relatively limited compared to their performance in treating hematological malignancies. 

 

Tumor heterogeneity involves diverse subclones with distinct genomic alterations and antigenic profiles, making it difficult for targeted therapies to uniformly eliminate all cancer cells. Additionally, it is widely recognized that intrinsic heterogeneous antigen expression and antigen escape during treatment can contribute to limited outcomes of molecular targeting therapies.  

 

Meanwhile, the immunosuppressive environment is created by the recruitment of suppressive immune cells, which produce inhibitory factors including cytokines and immune checkpoint molecules. This complex ecosystem further hampers the immune system's ability to mount an effective response against solid tumors. 

 

Unlike immune checkpoint inhibitors like anti-PD-1/PD-L1 antibodies that can invigorate intrinsic antigen recognition system of T cells, T cell based-therapy such as TCE and CAR-T may be susceptible to tumor heterogeneity and the suppressive TME. Along with direct T-cell recruitment to tumor sites, the accomplishment of alleviating immunosuppressive TME or overcoming heterogeneity, or both, could be the rational strategy to enhance the efficacy of conventional TCE and CAR-T therapy. 

 

By understanding the intricate interplay between tumor cells, immune cells, and the TME, and by focusing on approaches that tackle tumor heterogeneity and/or improve the immunosuppressive environment, we can pave the way for the development of more effective immunotherapies for patients with solid tumors.

What we're looking for

We are looking for technologies to improve the efficacy and/or enhance multifunctionality of multi-specific antibody or CAR-T as single agents. Our focus is on two key areas, 1) to alleviate the immunosuppressive tumor microenvironment (TME), and 2) to overcome heterogeneity of solid tumors by leveraging host immune responses against tumor neoantigens.

Solutions of interest include:
  • Technologies for modulating the innate immune systems to induce T cell responses against heterogeneous solid tumors, such as innate immune activators and antigen spreading enhancers.
  • Technologies for modifying the immunosuppressive TME to activate anti-tumor immunity, such as tumor-associated macrophages (TAM) reprogramming, and novel immune checkpoint inhibitors.
Our must-have requirements are:
  • Proposals should include a strong hypothesis and scientific rationale for how the technology will alleviate immunosuppression within the TME and/or activate the innate immune system to induce T-cell responses against heterogeneous tumors, accompanied by a plan to validate these effects in vivo.
Our nice-to-have's are:
  • In vivo data demonstrating that the technology activates the innate immune system to induce T-cell responses against heterogeneous tumors.
  • In vivo data demonstrating that the technology alleviates and/or converts immunosuppression within TME.
  • Data demonstrating that the underlying mechanisms and/or targets of the technology are conserved between experimental models in animals and humans.
  • Information on tumor specificity and organ specificity of target molecules and/or mechanisms.
What's out of scope:
  • Technologies that act on the mechanism/targets of T cells to simply enhance T cell activity.
  • Combination approaches that rely on the synergistic effects of different types of therapies (e.g. small molecule inhibitor in combination with a CAR-T therapy or multi-specific antibody).
Acceptable technology readiness levels (TRL):
Levels 2-5
What we can offer you
Eligible partnership models:
Sponsored research
Benefits:
Sponsored Research
Funding is proposal dependent, with up to $ 150K for 12 month project with potential follow-on funding for 1 year.
Expertise
Partners will be assigned a company mentor to champion the project, and meet once every 3-4 months to ensure project success.
Who we are

At Daiichi Sankyo, we attach significant importance to working with academic institutions, startups and bioventure companies to discover new therapeutics in the place where hypotheses are brought and tested in order to expand possibilities for scientific innovation breakthrough. We build sustainable relationships with partner institutions and companies through open and fair alliance management and trust based on mutual respect as the foundation for effective collaborations. Our goal is to jointly create new value for patients by maximizing each other’s expertise and strengths.

https://www.daiichisankyo.com/rd/strategy_operations/open_innovation/

 Learn more
Reviewers
MN
Masatoshi Nagamochi
Associate Director
MK
Mikio Kato
senior director
IK
Isao Kaieda
Associate Director
TT
Takayuki Tatamiya
Senior Director
JI
Jun Ishiguro
Researcher
RF
Rikiya Fukasawa
Researcher
CS
Chikako Suzuki
director
Q&A with Daiichi Sankyo

The Q&A is now closed.

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Most upvoted
Q.
Does the technology described in these papers (ablation of the transcription factor IRF4) fit your requirements? 1.) Zou D. et al., Nature Immunology volume 25, pages 66–76 (2024) 2.) Yan H. et al., iScience, Vol 26, Issue 11, 17 Nov 2023, 108087 3.) Yu A. et al., Research 17 Nov 2023 Vol 6 Article ID: 0271
JS
John Schultz, Tech Transfer, Houston Methodist
September 3, 2024
1
A.
Thank you very much for your question. The technology that simply enhance T-cell activity is out of focus because our focus is on two key areas, 1) to alleviate the immunosuppressive tumor microenvironment (TME), and 2) to overcome heterogeneity of solid tumors by leveraging host immune responses against tumor neoantigens.
RF
Rikiya Fukasawa, Researcher, Daiichi Sankyo
September 4, 2024
Is this response helpful?
0
0
Q.
Would you be interested in inhibition of TREM-1 and/or TREM-2 expressed on tumor-associated macrophages in order to modify the immunosuppressive TME?
1
A.
Do you have the strategy in which the inhibition of TREM-1 and/or TREM-2 apply for multi-specific antibody or CAR-T modalities? If you picture the combination therapy using small molecule, peptide or something, it's out of scope.
RF
Rikiya Fukasawa, Researcher, Daiichi Sankyo
September 5, 2024
Is this response helpful?
0
0
Q.
Does immunostimulatory CpG fall into your scope? Not so clear about your exclusion scope. Thanks if answer will be available.
1
A.
Thank you for the question. Do you have the strategy in which CpG apply for multi-specific antibody or CAR-T modalities? We are looking for technologies to improve the efficacy and/or enhance multifunctionality of multi-specific antibody or CAR-T "as single agents". If you picture the combination therapy , it's out of scope.
JI
Jun Ishiguro, Researcher, Daiichi Sankyo
September 30, 2024
Is this response helpful?
0
0
Q.
Does a technology to modulate antigen presentation, leading to enhanced neoantigen presentation and enhancement of NK cell responses fit your requirements?
1
A.
Thank you very much for your question. That's one of the technologies we're looking for. We would also like to remind you that the ability to incorporate the technology into CAR-T and multispecific antibodies is an additional requirement.
RF
Rikiya Fukasawa, Researcher, Daiichi Sankyo
October 9, 2024
Is this response helpful?
0
0
A.
Thank you for the quick response. Our expertise revolves around modulating the activity of ER aminopeptidase 1, an ER enzyme that prepares or destroys antigenic peptides. We have developed inhibitors for this purpose, including some in late pre-clinical stage, and have expertise in evaluating their efficacy in in vitro and in vivo systems. I can go ahead and submit a proposal, but I may be helpful to talk first to better understand your needs.
1
Q.
Is this potentially of interest? We use a strong adjuvant injected intra-tumourally to overcome TME immunosupression. Have tested in phase I trial in cancer patients. https://jitc.bmj.com/content/9/9/e002688.long
1
A.
Thank you for your question. We are seeking technologies that can improve the efficacy and/or enhance the multifunctionality of multi-specific antibody or CAR-T when used as single agents. Therefore, if your strategy focuses on combination therapy, it's out of scope.
RF
Rikiya Fukasawa, Researcher, Daiichi Sankyo
October 22, 2024
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