Distinguishing Cancer Cells From Normal Cells
What is Chromosomal Instability
During the process of tissue growth, each human chromosome is replicated with high fidelity, and cell division (mitosis) gives rise to genetically identical daughter cells, in which the structure and number of chromosomes is faithfully maintained.
In cancer cells, defects in the mechanisms controlling replication and mitosis lead to chromosomal instability (CIN), in which the frequency of gain or loss of whole or partial chromosome fractions is greatly increased.
CIN uniquely distinguishes cancer cells from normal cells, and CIN has been shown to be a fundamental driver of tumor progression and metastasis in specific instances.
iCAR Dual Targeting Technology
ImmPACT Bio is developing a dual CAR-targeting platform that programs T cells to recognize the genetic consequences of chromosomal instability (CIN) in all cancers.
Our unique technology is specifically designed to detect loss of target gene expression, enabling the killing of cancer cells without damaging normal tissues.
We are focused on gene targets that are either irreversibly lost due to direct deletion or mutational inactivation, or deleted due to unbalanced chromosomal rearrangements, gene conversion, mitotic recombination, or whole chromosome monosomy.
In targeting genetically determined loss of gene expression, specific to cancer cells, the ImmPACT Bio dual CAR-targeting platform circumvents the fundamental barrier of target selectivity in developing potent CAR T cell therapy to treat solid tumors.
Here is how our iCAR technology works
T-cell inhibition - Protection
Normal tissue has a dual expression of both alleles. These alleles are the CAR antigens.
In the context of the normal tissue, activation of the canonical CAR (aCAR) is diminished by the co-expression of the inhibitory CAR (iCAR) target on that tissue. The normal tissue is spared.
T-cell activation - Killing
Tumor tissue has lost the expression of the iCAR antigen due to chromosomal instability. This loss is irreversible and the inhibitory interaction is also lost.
In the context of the tumor tissue, activation of the canonical CAR (aCAR) is enabled and the tumor cells are eliminated.
T-cell inhibition - Protection
Normal tissue has a dual expression of both alleles. These alleles are the CAR antigens.
In the context of the normal tissue, activation of the canonical CAR (aCAR) is diminished by the co-expression of the inhibitory CAR (iCAR) target on that tissue. The normal tissue is spared.
T-cell activation - Killing
Tumor tissue has lost the expression of the iCAR antigen due to chromosomal instability. This loss is irreversible and the inhibitory interaction is also lost.
In the context of the tumor tissue, activation of the canonical CAR (aCAR) is enabled and the tumor cells are eliminated.
