Our therapy tries to address the following problems of CAR T-cell therapy and in a broader sense, with regards to cancer therapy itself.

  • CAR T therapy fails when it encounters multiple antigens because it cannot penetrate metastasized tumor masses
  • As a consequence, it is rendered ineffective against solid tumors
  • Chemotherapy has a lot of unwanted side effects as the drug kills lot of ‘bystander’ and immune cells, which leads to the patient being even more weak
  • CAR T treatment’s cytotoxicity which has showed up during patient clinical trials
  • Overall expense of CAR T treatment

All of these questions have primarily been answered via exhaustive literature review and modeling studies, apart from talking to domain experts on these issues. Working with CAR T-cells was an ambitious, yet proposition from the beginning, but we aim for this research to be carried out by using actual CAR T-cells in the future, and the research and proof of concept we aim to give is based on this very fact.

What about Multiple Antigens?

Our therapy seeks to address this by the usage of a drug which acts on the very thing that holds tumors together - i.e. the adhesion molecules, which allows the CAR T - cell therapy to work better. This has been adequately demonstrated by our Math Model, as procuring CAR T-cells and working with them wasn’t possible for us.

Figure 1: Tumor having multiple tumor-associated antigens present on surface, ultimately causing antigen escape - where tumor cells become resistant to therapy1 (Created using BioRender)

Why Solid Tumors?

Solid tumors have a problem of having multiple antigens on its surface, so CAR T-cells aren’t able to penetrate them2. Our solution to this problem is to bypass the antigenic-heterogeneity problem itself, and focus on getting more surface area for the CAR to target tumors.

Side effects of Chemotherapy - worth the risk?

Studies show that the remission rate of chemotherapy is very low in case of leukaemia (a meagre 38%) as compared to CAR T-cell therapy (90.7%)3. But we’re not able to reach that stage of trials, because CAR T-cell therapy against solid tumors is itself very primitive and isn’t well established. On top of that, the side effects associated with chemotherapy isn’t something to be brushed aside, as normal cell death via tumor-associated drugs can cause further weakening of the already weakened immune system. We seek to change the approach to this by binding the drug to a receptor so that it stays in contact with our delivery vehicle at all times, and doesn’t cause adverse effects to other cells during its journey. We ensure this via a two step failsafe:

  • Drug had extremely high binding scores to the receptor (Refer to our Docking Studies)
  • The antagonist to the receptor has even higher docking scores and even binds to the same binding pocket as the drug - so serves as an immediate competitor to the drug, which causes the drug to unseat itself from its binding pocket and go on to target tumor masses

This implementation ensures that the side effects of the drug are minimalized to every possible extent.

Cytotoxicity of CAR T - cells

CAR T-cells elicit an enhanced immune response by using their signaling domain to ‘call’ more T - cells. But a very common adverse effect of this is a cytokine storm4 as a result of the dosage of the treatment, with an extremely adverse effect of this treatment being Leukoencephalopathy5. All of this is a result of high dosage of CAR T-cells inside the body, which conditions the body to an enhanced immune response for minor inflammations. As a solution to this, based on our Math Model studies (link to math model), we show that with the help of our modified treatment, we reduce the concentration CAR T-cells as well as the dosage required for the tumor to go into remission. Thus, this helps the body to remain functional even after a very high-impact immunotherapy.

Expense associated with CAR T treatment

It is already known that CAR T being such an experimental form of therapy results in it being inaccessible to the common man. Treatment can easily cost millions of dollars because of the high dosage given. In order to counter this, our treatment focuses on reducing the overall cost of therapy by reducing the number of CAR T-cells required for NSCLC to go into remission.

Overall Implementation

CAR T can be given intravenously, and the injection of ‘seeker’ T-cells having the honokiol attached to them can be done a few days before starting the CAR T cell treatment so as to maximize efficiency. AM 6538 can also be delivered into the bloodstream after a period 14 - 18 hours after the injection of T cells bound to honokiol.

Delivery of AM - 6538

As AM - 6538 is also a small molecule, we have theorized for it to be sent by one of two mechanisms:

  • A biocompatible nanocarrier - based delivery system, which is highly specific to the tumor in question6, so the antagonist directly travels to the site of action.
  • The antagonist could possibly be placed in a biodegradable suture-based microsphere, and that can be used for targeted delivery7.


[1] Mirzaei, H.R., Rodriguez, A., Shepphird, J., Brown, C.E. and Badie, B., 2017. Chimeric antigen receptors T cell therapy in solid tumor: challenges and clinical applications. Frontiers in immunology, 8, p.1850.(Link)

[2] Safarzadeh Kozani, P., Safarzadeh Kozani, P., Ahmadi Najafabadi, M., Yousefi, F., Mirarefin, S.M.J. and Rahbarizadeh, F., 2022. Recent advances in solid tumor CAR-T cell therapy: driving tumor cells from hero to zero?. Frontiers in Immunology, 13, p.795164. (Link)

[3] Wei, G., Hu, Y., Pu, C., Yu, J., Luo, Y., Shi, J., Cui, Q., Wu, W., Wang, J., Xiao, L. and Wu, Z., 2018. CD19 targeted CAR-T therapy versus chemotherapy in re-induction treatment of refractory/relapsed acute lymphoblastic leukemia: results of a case-controlled study. Annals of hematology, 97, pp.781-789. (Link)

[4] Santomasso, B., Bachier, C., Westin, J., Rezvani, K. and Shpall, E.J., 2019. The other side of CAR T-cell therapy: cytokine release syndrome, neurologic toxicity, and financial burden. American Society of Clinical Oncology Educational Book, 39, pp.433-444. (Link)

[5] Sdrimas, K., Diaz-Paez, M., Camargo, J.F. and Lekakis, L.J., 2020. Progressive multifocal leukoencephalopathy after CAR T therapy. International journal of hematology, 112, pp.118-121. (Link)

[6] Wu, P., Han, J., Gong, Y., Liu, C., Yu, H. and Xie, N., 2022. Nanoparticle-Based Drug Delivery Systems Targeting Tumor Microenvironment for Cancer Immunotherapy Resistance: Current Advances and Applications. Pharmaceutics, 14(10), p.1990. (Link)

[7] Vasir, J.K., Tambwekar, K. and Garg, S., 2003. Bioadhesive microspheres as a controlled drug delivery system. International journal of pharmaceutics, 255(1-2), pp.13-32. (Link)