CGT Insights Anocca.pdf

Co-founder CEO Reagan Jarvis, writes in Cell & Gene Therapy Insights on the importance of systemization in T‑cell therapy development and how Anocca’s platform is uniquely built to address these challenges. In the article Jarvis highlights TCR‑T cell therapies potential to effectively target solid tumours, an area where CAR‑T therapies have historically struggled due to lack of relevant cancer targets

Systemization is key to fulfilling T cell therapy’s promise in cancer

Anocca Raises SEK 440 Million to Advance Clinical Trial Targeting Pancreatic Cancer

The TCR-T cell therapies of tomorrow

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Dysregulated Gene

Driver Mutation

Onco-viral

A*11:01 : G12V

A*11:01 : G12D

A*03:01 : G12V

Other HLAs : G12V

Other HLAs : G12D

Other Mutations

KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog), plays a crucial role in human cell signaling pathways. KRAS acts as a molecular switch in the MAPK/ERK pathway to regulate cell proliferation, differentiation, and survival. Mutations in KRAS can lead to uncontrolled cell growth, most of which are “Driver Mutations”, causing the development of multiple cancers.

Basic Info

KRAS

A*02 : R175H

The p53 protein plays a pivotal role in regulating cell cycle, DNA repair, and apoptosis to prevent genetic mutations and cancer development. As a transcription factor, it responds to DNA damage by either halting cell division to allow for repair or initiating programmed cell death if the damage is irreparable. Mutations in p53 are found in over half of all human cancers, underscoring its critical role in protecting cells from becoming cancerous.

A*02:01 : P29S

RAC1, a member of the Rho family of GTPases, is a crucial signaling molecule that regulates a wide array of cellular processes including actin cytoskeleton organization, cell growth, migration, and survival. Dysregulation of RAC1 activity is implicated in various pathological conditions, including cancer progression and metastasis.

RAC1

A*02:01

Other HLAs

PRAME (Preferentially Expressed Antigen in Melanoma) is a cancer-testis antigen that plays a role in the regulation of gene expression and immune response modulation. While its precise cellular functions are still being elucidated, PRAME is known to be involved in repressing retinoic acid signaling, a pathway crucial for cell differentiation and growth. This protein is typically expressed at low levels in normal tissues but is upregulated in various malignancies, including melanoma, leukemia, and several solid tumors.

PRAME

A*24

B*07

MAGE-A4 is a member of the MAGE (Melanoma Antigen Gene), involved in regulating key cellular mechanisms such as apoptosis and cell cycle control, although its exact function remains partially understood. Like its counterparts, MAGE-A4 is predominantly expressed in a wide range of cancers while being minimally present in normal tissues, making it an attractive candidate for cancer diagnostics and targeted therapies. Its involvement in cancer progression and potential role in immune system evasion underscore the therapeutic interest in targeting MAGE-A4 in oncology.

MAGE-A4

A*01:01

MAGE-A3 is a member of the MAGE (Melanoma Antigen Gene), characterized by its selective expression in cancer cells compared to normal tissues. It plays a role in the alteration of apoptotic pathways and immune recognition, contributing to tumor cell survival and proliferation. MAGE-A3 has been extensively studied as a target for cancer vaccines, especially in melanoma and non-small cell lung cancer, due to its immunogenic properties and prevalence in various tumor types.

MAGE-A3

MAGE-A1 is a member of the MAGE (Melanoma Antigen Gene) family, known for its role in immune evasion and cancer progression. This protein is typically silent in most normal adult tissues but becomes aberrantly expressed in a variety of cancers, including melanoma, breast, and lung cancers. MAGE-A1's function in tumorigenesis is still under investigation, but it is believed to modulate key cellular processes like apoptosis and cell cycle regulation. Its cancer-specific expression profile makes MAGE-A1 a promising target for cancer immunotherapy and vaccine development.

MAGE-A1

MAGE-A10 is a member of the MAGE (Melanoma Antigen Gene), known for its cancer-specific expression pattern, particularly in melanoma, lung, and bladder cancers. The protein is implicated in crucial cellular processes that contribute to tumor growth and metastasis. Although the precise mechanisms of MAGE-A10's action are not fully understood, its restricted expression in tumors versus normal tissues positions it as a valuable target for cancer immunotherapy approaches, including vaccines and adoptive T-cell therapies, aimed at eliciting a specific immune response against cancer cells expressing MAGE-A10.

MAGE-A10

NY-ESO-1, also known as Cancer/Testis Antigen 1B (CTAG1B), is a prominent member of the cancer-testis antigen family, characterized by its restricted expression to the testis in normal adult tissues and aberrant expression in a wide range of cancers, including melanoma, sarcoma, bladder, and esophageal cancers. The expression of NY-ESO-1 in tumors but not in most normal tissues makes it an attractive target for therapeutic cancer vaccines, T cell receptor-engineered T cell therapies, and other forms of immunotherapy.

NY-ESO-1

The E7 protein, produced by high-risk HPV strains, acts as a viral oncoprotein by binding to and inactivating the retinoblastoma protein (pRb), a critical tumor suppressor. This interaction releases E2F transcription factors, promoting cell cycle progression and unregulated cell division. E7's disruption of the pRb pathway allows infected cells to evade normal growth controls, contributing significantly to the oncogenic transformation process and the development of cancers associated with HPV infection.

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Systemization is key to fulfilling T cell therapy’s promise in cancer

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