CAR-T 
GIMI uses patented advanced 4th generation CAR design (4SCAR) with high efficacy and minimal side-effect (cytokine releasing syndrome – CRS). For many years GIMI has developed multiple different target CARs for blood cancer and solid tumors.

EIE 
Engineered Immune Effector (EIE) is tailor-made targeted immune cells for each patient. EIE recognizes multiple specific tumor-associated antigens and then exerts immune effector functions to kill tumor cells or pathogens (targeting virus and fungal infections, etc.).

Dendritic Cell (DC) Vaccines
Using the latest technology (NGS WES and computer-aided HLA restricted epitope prediction technology) including immune gene-modified tumors to modify Dendritic Cells (DC) to produce immune gene-modified DC vaccines. 

Neoantigens or Neoepitopes
Neoantigens (Neoepidopes) are cancer-specific antigens based on the mutations particular to a cancer by using advanced sequencing technology to discover the difference between the DNA of a tumor and a patient’s normal cells. This is one of the newest tools in cancer immunotherapy. Because neoantigens target only the tumor, they tend to have less non-specific side effect. Neoantigens can be used in EIE and DC technologies.

GIMI´s portfolio offers powerful advantages
GIMI’s immune portfolio options amplify the power of traditional immunotherapy by engaging adaptive and innate immune systems, directly and indirectly, with multi-target gene-associated anti-cancer immune strategies.

Challenges for CAR-T cells in solid tumors and Acute Myeloid Leukemia
The two main challenges that CAR/TCR T-cell face in solid tumors are the heterogenous expression and escape of the CAR/TCR target antigens and local immunosuppression that impedes their clinical implementation:

1. Tumor target antigen heterogeneity
Heterogenous antigen expression or loss on tumor cells increases the risk of antigen-escape and the formation of CAR-T resistant tumors.

2. Immunosuppressive tumor microenvironment
The microenvironment of solid tumors and AML is highly immunosuppressive, which exhausts the CAR-T cells and makes it more difficult for them to infiltrate tumors, thus limiting their potential to kill cancer cells.

Multi-antigen targets - GIMI´s technology
GIMI´s technology utilizes a multi-antigen CAR-T cell accordingly to tumor gene expression. The multi-antigen approach has been well-tolerated and shown to enhance tumor-killing capability with prolonged efficacy.

Choosing the right technology
Selecting the right technology is on a case-by-case basis. Generally, the immune system as a result of cancer or chemotherapy will benefit more from CAR-T and EIE and less from DC. This is because CAR-T and EIE technologies can expand and greatly increase the immune cells in culture.

The intact immune system can benefit from all technologies, with DC being the easiest and cheapest one with few side effects.

The choice of immune cell technology is also based on testing results, and the best options may depend on the type of target antigens and the individual condition.

Testing for the right antigen target
In order to design the best cell technology against the specific tumor, tumor testing must first be performed unless the target antigens are well known. Our service comprehensively analyzes antigen repertoire using blood and tissue samples' most advanced technology (Flow Cytometry [FACS], Immunohistochemistry [IHC] staining, next-generation sequencing [NGS], and RT-pPCR/ddPCR). A detailed data analysis will be performed to study which antigens are more suitable for immune technology. We ensure that we consistently perform this service, from sample preparation to delivering results.

Manufacturing
GIMI’s manufacturing process is the school of immune cells. The first step is to harvest cells from blood and separate the cells required for each technology.

CAR-T technology – 1 week of preparation time.
EIE technology – 20 days of preparation time.
DC vaccine technology – 5 days of preparation time.

All types of Adoptive Cell Technology require an initial blood cell draw, called apheresis. In solid tumors, the sample is processed to analyze antigens presence and/or processed to obtain antigens peptides to produce EIE or DC vaccine.