The SPICA Technology

The SPICA Technology

At Immugenia, we have created a biotechnological tool enabling the use of hematopoietic stem cells to treat life-threatening cancers. Our SPICAs (Specific Promoters for Immune Cell Activity) are a variety of synthetic promoters that drives the expression of a gene only in intended cells, thereby adding selectivity and allowing the use of stem cells for therapy.

A promoter is a sequence that turns a gene on/off. Those promoters dictate which proteins are expressed in a given cell, allowing for a cell to be specialized in its function. When a cell is genetically modified with a CAR or another added gene, the new gene is expressed in all types of cells because the used promoter is not tailored to be selective. This precludes the use of stem cells for immunotherapy. Immugenia has solved this technological roadblock and unlocked the power of stem cells.

At Immugenia, we have created a biotechnological tool enabling the use of hematopoietic stem cells to treat life-threatening cancers. Our SPICAs (Specific Promoters for Immune Cell Activity) are a variety of synthetic promoters that drives the expression of a gene only in intended cells, thereby adding selectivity and allowing the use of stem cells for therapy.

A promoter is a sequence that turns a gene on/off. Those promoters dictate which proteins are expressed in a given cell, allowing for a cell to be specialized in its function. When a cell is genetically modified with a CAR or another added gene, the new gene is expressed in all types of cells because the used promoters is not tailored to be selective. This precludes the use of stem cells for immunotherapy. Immugenia has solved this technological roadblock and unlocked the power of stem cells.

Therapeutic Strategy

One immunotherapy for life

Therapeutic Strategy

One immunotherapy for life

Chimeric Antigen Receptors (CAR) are molecule tailored to recognize tumor cells and trigger its death.

Traditionally CAR are put into T cells as these white blood cells have a capacity to kill other cells. Impressive results have been obtained with patients suffering from leukemias and lymphomas, but the technology is still in its infancy and needs to be improved to face its numerous current limitations.

At Immugenia we are creating CAR therapies based on the modification of hematopoietic stem cells, the cells that give rise to all the blood cells, white (immune) and red. Everyone, even patients going through aggressive regiment of chemotherapy, have hematopoietic stem cells that are easily harvestable to be modified.

Once transplanted back in their body, patients will produce their own CAR T and NK cells. Since stem cells have the ability to self-renew and to give rise to progeny for life, this therapy would be “One immunotherapy for a lifetime!”

Chimeric Antigen Receptors (CAR) are molecules tailored to recognize tumor cells and trigger their death.

Traditionally CAR are put into T cells as these white blood cells have a capacity to kill other cells. Impressive results have been obtained with patients suffering from leukemias and lymphomas, but the technology still faces some challenges reducing its efficacy in the long term and causing side effects.

At Immugenia we are creating CAR therapies based on the modification of hematopoietic stem cells, the cells that give rise to all the blood cells, white (immune) and red. Everyone, even patients going through aggressive regiment of chemotherapy, have hematopoietic stem cells that are easily harvestable to be modified.

Once HSCs have been engineered, patients will produce their own CAR T and NK cells. Since stem cells have the ability to self-renew and to give rise to progeny for life, this therapy would be “One immunotherapy for a lifetime!”

Current challenges in CAR T-cell therapy

1
Gradual Loss

Relapses due to loss of CAR-T cells over time

2
High Toxicity

Cytokine release syndrome might complicate treatment and lead to neurotoxicity

3
Reduced Efficacy

High expression of the CAR results in T-cell exhaustion

Current challenges in CAR T-cell therapy

1
Gradual Loss

Relapses due to loss of CAR-T cells over time

2
High Toxicity

Cytokine release syndrome might complicate treatment and lead to neurotoxicity

3
Reduced Efficacy

High expression of the CAR results in T-cell exhaustion

4
CAR T-Cell Production

Difficulty to engineer CAR-T cells in patients with a low count of T cells due to chemotherapy

5
Cold Tumors

Limited efficacy in solid tumors due to challenges in the tumor microenvironment

Advantages of HSC-based immunotherapies

1
Persistence

Persistence through the constant arrival of CAR bearing cells from HSC differentiation

2
Relapse Patrol

Gradual replenishment of T cells maintains optimal activity and allows for the perpetual surveillance of relapses

3
Safety

Safer by preventing
cytokine release syndrome and neurotoxicities

Advantages of HSC-based immunotherapies

1
Persistence

Persistence through the constant arrival of CAR bearing cells from HSC differentiation

2
Relapse Patrol

Gradual replenishment of T cells maintains optimal activity and allows for the perpetual surveillance of relapses

3
Safety

Safer by preventing
cytokine release syndrome and neurotoxicities

4
Availability of HSCs

HSCs are found in sufficient quantity to be engineered as they are less affected by chemotherapy treatments

5
Synergistic Effect

No need to choose between CAR-T or CAR-NK because they are both leveraged, in one product, to fight solid tumors

In vivo CAR delivery

The future of CAR therapy

In vivo CAR Delivery

The future of CAR therapy

While CAR-T therapy has demonstrated effectiveness, its widespread adoption is constrained by high costs, the need for personalized treatment, and the complexities of ex vivo cell modification. A promising approach to improve accessibility is to replace the ex vivo modification and expansion process with an in vivo method. This involves systemically administering a virus that transduces T, NK or HSC to express CARs directly within the patient’s body.

Various gene therapy delivery vehicles have been developed for this purpose. However, to date, only a few have achieved adequate specificity in targeting the desired cells, posing a risk of unintended genetic modification in other organs, such as the liver.

At Immugenia, our advanced synthetic promoter technology allows for targeted expression of the transgene in specific cell types. This innovation could be the crucial element needed to make in vivo CAR delivery feasible. By combining these synthetic promoters with lentiviral-type delivery systems targeting immune cells, we aim to enhance the specificity of CAR expression, even if the delivery system inadvertently enters the wrong cells (off-target), thereby enabling safer in vivo CAR delivery.

No need for a perfect drug delivery system
for specific gene expression

Mobilisation triggering hematopoietic stem cell (HSC) circulation

Therapy administration:
Delivery System
(CAR + SPICA + Vehicule)

Engenieered
&
regular HSCs

Benefits

1
Reduces
Costs

2
Shortens
Waiting Times

3
Increases
Availability

4
Enhances safety of
in vivo Delivery

While CAR-T therapy has demonstrated effectiveness, its widespread adoption is constrained by high costs, the need for personalized treatment, and the complexities of ex vivo cell modification. A promising approach to improve accessibility is to replace the ex vivo modification and expansion process with an in vivo method. This involves systemically administering a virus that transduces T, NK or HSC to express CARs directly within the patient’s body.

Various gene therapy delivery vehicles have been developed for this purpose. However, to date, only a few have achieved adequate specificity in targeting the desired cells, posing a risk of unintended genetic modification in other organs, such as the liver.

At Immugenia, our advanced synthetic promoter technology allows for targeted expression of the transgene in specific cell types. This innovation could be the crucial element needed to make in vivo CAR delivery feasible. By combining these synthetic promoters with lentiviral-type delivery systems targeting immune cells, we aim to enhance the specificity of CAR expression, even if the delivery system inadvertently enters the wrong cells (off-target), thereby enabling safer in vivo CAR delivery.

No need for a perfect drug delivery system
for specific gene expression

Mobilisation triggering hematopoietic stem cell (HSC) circulation

Therapy administration:
Delivery System
(CAR + SPICA + Vehicule)

Engineered
&
regular HSCs

Benefits

1
Reduces Costs

2
Shortens Waiting Times

3
Increases Availability

4
Enhances Safety of in vivo Delivery