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Science overview

What are hot and cold tumors?

Solid tumors are cancers that form a mass or lump of abnormal cells, such as breast, lung, colon, and pancreatic cancers. They account for about 90% of adult cancers. Solid tumors can be described as “hot” or “cold” based on how the immune system responds to them.

Hot tumors contain many active immune cells and are generally more responsive to immunotherapy. Cold tumors have few cancer-fighting immune cells and are more difficult for the immune system to recognize and attack. While there is no universal percentage, most solid tumors are considered immunologically cold or poorly inflamed, making “turning cold tumors hot” an important goal of cancer research.

TIL therapy

TIL – a natural immune response to treat cancer

TILs are immune cells that recognize, attack, and kill cancer cells. TILs recognize cancer cells through tumor antigens expressed on the surface of cancer cells that are unique to each person. When cancer grows and metastasize, TILs lose their ability to perform their intended function. Ineffective TILs give the tumor cells a chance to evade the immune system and grow.

How TIL & TCR-T therapies work

By strengthening the patient’s own immune response cancer can be treated. Investigational treatments have demonstrated complete and durable remission in a range of solid cancer tumors with both TIL- and TCR-T-based therapies (Receptor-modified T-cells). In polyclonal TIL therapy a patient’s naturally occurring TILs are collected through tumor biopsy, grown ex-vivo and then infused back to the patient. To target specific antigens, the T-cell receptor (TCR) can be modified to make them more reactive before expanded ex-vivo from the patient’s own peripheral blood.

Next-generation TIL

Enhancing stemness and TCR diversity to improve anti-tumor activity

2. Standard expansion

Cell product characteristics: high differentiated T cells with loss of tumor antigen specific clonotypes. Low TCR diversity. Tumor survival.

Standard expansion protocols are effective to treat hot tumors only.

Tumor-reactive cells isolation and gene-editing protocols are lengthy, hard to scale and expensive.

3. CytoPLY™

Cell product characteristics: stemlike T cells with polyclonal tumor antigen specificity. High TCR diversity. Tumor eradication.

CytoPLY™ enables tailored TIL expansion through refined process engineering to generate potent, tumor-reactive T cells capable of overcoming cold tumor microenvironments.

T naive to T effector: more differentiated. Adapted from Kishton et al, 2022, Curr Opin Immun · sciencedirect.com

Illustration: polyclonal T cells are expanded in two ways. Standard expansion gives highly differentiated T cells with low TCR diversity, and the tumor survives. CytoPLY™ gives stemlike T cells with high TCR diversity, and the tumor is eradicated.

CytoPLY™ pioneers next generation T-cell immunotherapy

CytoPLY™ is an advanced T-cell activation and enrichment platform that amplifies cytotoxicity, unlocking revolutionary opportunities in T-cell therapy such as polyclonal TIL and monoclonal TCR-T.

Stronger

Produces T-cells with enhanced functionality, through increased persistence and increased cytokine production.
Broader

Preserves and expands diverse TCR repertoires, targeting a wider range of tumor antigens.
Faster

Accelerates T-cell expansion, achieving higher cell numbers in less time compared to conventional expansion protocols based on IL-2 alone.

CuraCell’s first product, CC-38, targets prostate cancer and colorectal cancer

CuraCell’s first generation product is a TIL with amplified cytotoxicity from CytoPLY™. A proprietary dosing regime combined with checkpoint inhibition ensures a synergistic and lasting response as well as a more gentle pre-treatment of the patient.

Patient-named treatments of CC-38 show promising results. Complete and partial responses across a diverse group of cold solid tumor patients demonstrate the potency and broad applicability of CC-38. In its first clinical program CC-38 targets late-stage prostate cancer and colorectal cancer with a vast unmet medical need.