Our novel approach to treating solid tumors

Recent genetic engineering advances have made it possible to manipulate human immune cells for the treatment of cancer. T cells engineered to express a tumor-recognizing receptor have shown outstanding success in hematologic malignancies but such results have not translated to solid tumors.

We believe that our approach can overcome hurdles historically encountered in the treatment of solid tumors by engaging both the innate and adaptive immune systems to launch a multi-pronged attack against cancer.

Problem -
Cancer Evades Immune Destruction		Our Solution -
Chimeric Antigen Receptor Macrophage (CAR-Macrophage)
Immune cell trafficking
Tumors control which immune effector cells have access to their microenvironment.		Myeloid cell biology
Monocytes and macrophages are actively recruited to solid tumors.
Heterogeneity
Every cancer is unique. There is significant cell-to-cell heterogeneity within a tumor mass, allowing for the development of resistance to single-antigen targeted therapies.		Antigen presenting cell
Unlike other cell types utilized in CAR cell therapy, macrophages are professional antigen presenting cells, capable of leading to activation of the patient’s own adaptive immune system.

Thus, Carisma’s approach allows for therapeutic efficacy beyond the antigen target which the CAR is designed to engage.
Immunologically cold tumors
Leukocytes, such as T cells, are often prevented from penetrating the tumor tissue, leading to immunologically cold tumors that fail to respond to immune therapies.

Infiltrating immune cells are susceptible to potent immunosuppression.		Anti-tumor (M1) polarization
Carisma’s CAR-Macrophages are polarized toward an anti-tumor, or M1, macrophage phenotype, and upregulate genes that can enhance the activation/recruitment of immune cells (such as T cells).

Carisma’s CAR-Macrophages are restricted to an anti-tumor phenotype.
Tumor associated macrophages
Current macrophage-minded immuno-oncology approaches rely on the function of intratumoral, immunosuppressed tumor-associated macrophages.		Adoptive transfer of fine-tuned,
engineered macrophages
Carisma adoptively transfers genetically engineered CAR macrophages – active tumor-killing cells whose properties have been fine-tuned in the laboratory.

Addressing the key challenges of
treating solid tumors

Unlike other immune cells, our CAR-Macrophages combine a unique set of characteristics, which we believe are the key to success in solid tumor treatment:

  • Recruitment and access to the solid tumor microenvironment with the capacity to selectively destroy cancer cells
  • Ability to survive in the hostile solid tumor setting and maintain an anti-tumor phenotype in the presence of immunosuppressive factors
  • Activation of an adaptive immune response leading to long-term anti-tumor immunity and protection against antigen negative relapse

Carisma’s CAR-Macrophages in action

The word macrophage comes from the Greek terms “makro” meaning big and “phagein” meaning eat. Macrophages are a key player in the innate immune system, with the ability to selectively target and destroy multiple tumor cells over their lifespan. This video shows our CAR-Macrophages (in red) in action against cancer cells (in green).

Watch Video
carisma-engineered-cell-platform

A tunable cell therapy platform

Carisma’s engineered cell therapies rest on breakthrough platform technology that enables genetic manipulation of myeloid cells (including monocytes and macrophages) ex vivo and re-introduction into patients, enabling multiple therapeutic applications in and beyond oncology.

Our proprietary viral and non-viral delivery methods enable highly effective gene insertion, the ability to tune the phenotype of the macrophages into either proinflammatory or anti-inflammatory, in addition to delivering a variety of payloads, including cytokines and antibodies.

CT-0525_Manufacturing_Process_Final

A robust manufacturing process

Carisma’s core manufacturing technology is designed to be scalable, reliable, and flexible. It provides a manufacturing platform from which our comprehensive pipeline of engineered monocytes can be developed towards multiple therapeutic uses. With a rapid processing time of only one day, we are able to deliver personalized treatment to patients in a timely manner, recognizing that cancer doesn’t wait.

Additionally, our experienced team has worked with leading experts in the field to develop allogeneic engineered monocytes/macrophages that would provide the potential for an off-the-shelf product, enabling even more patients to benefit from our cell therapies.