Background
Cancer immunotherapy is a treatment that manipulates a person’s immune system to fight cancer. It is a powerful additional tool in cancer treatment that may lead to long-lasting and potentially permanent tumor disappearance. Immunotherapy drugs include checkpoint inhibitors and cell-based cancer immunotherapies.
Checkpoint inhibitors work by binding to and thwarting the function of checkpoint proteins that prevent immune system activation. Inhibition of checkpoint proteins stimulates the immune system and allows the T cells to eliminate cancer cells. The fundamental importance of checkpoint inhibitors is best reflected in the 2018 Prize in Physiology or Medicine jointly awarded to James P. Allison and Tasuku Honjo for their discovery of cancer immunotherapy by preventing negative immune regulation.
There are four forms of cell-based cancer immunotherapies, i.e., CAR T-cells, tumor-infiltrating lymphocytes (TIL) specific for autologous tumors, tumor vaccines, and oncolytic viruses. Cell-based cancer immunotherapies have demonstrated excellent efficacy in various hematological (leukemia, lymphoma, myeloma) and solid tumor malignancies in children and adult patients. Due to the combination of demonstrated effectiveness in select settings, innovation potential, and the unmet medical need, there is an immense interest in developing novel forms of cell-based cancer immunotherapies. At the time of this writing, the search for clinical studies at clinicaltrial.gov searching for “CAR T-cells,” “tumor-infiltrating lymphocytes,” “tumor vaccines,” and “oncolytic viruses” have yielded over 3800 registered studies. These therapies are investigated for treating leukemias, lymphomas, and practically all forms of solid tumors, such as cancers affecting breast, lung, colorectal, prostate, brain, skin, kidney, liver, bladder, head, neck, cervical, and ovarian cancer.
The Problem
The availability of cell-based cancer immunotherapies in Croatia is limited due to:
- the very high cost of about €350.000 for each cell preparation prevents the wider adoption,
- large pharma companies are not interested in including Croatia in CAR T-cell treatment programs,
- only one commercial CD-19 CAR T-cell product is available,
- It is approved for the treatment of relapsed acute B lymphoid leukemia in persons <20 years and adults with diffuse large B cell lymphoma in patients that have failed at least two lines of treatment only,
- TIL and tumor vaccines are not available.
Our Solution
Through a collaborative approach, the Foundation will bring four forms of cell-based cancer immunotherapies to clinical use, i.e.,
- CAR T-cells,
- Tumor-infiltrating lymphocytes (TIL) specific for autologous tumors,
- Tumor vaccines, and
- Oncolytic viruses
CAR T-cell therapy will be introduced in collaboration with Caring Cross and Croatian clinical partners to treat B cell-derived leukemia and lymphoma. The Caring Cross will provide a novel CAR that could bring a substantial medical benefit over the current therapies. The CAR T-cell production will be done in the existing facility at the Sisters of Charity Hospital. Patient selection and all treatments will be made at the Children’s Hospital Zagreb and the University Hospital Centre Zagreb.
The introduction of CAR T-cell therapies will be used to facilitate the introduction of CAR T-cells for other indications and other forms of cell-based cancer therapies. Notably, the Foundation has exclusive access to a novel oncolytic virus. It will be initially tested for the treatment of glioblastoma, a form of brain tumor with limited therapeutic options and 1-year survival of only 15%.
Project Benefits
The benefits of locally produced cancer immunotherapies include:
- Up to a 90% reduction in CAR T-cell product price,
- Due to the dramatically lower cost of CAR T-cell products, the treatment will be accessible to anyone in medical need,
- Faster availability (6-12 days vs. on average five weeks for a commercial preparation),
- The possible greater effectiveness of treatment because cellular preparations will not undergo a cycle of freezing and thawing,
- Reducing the frequency of severe adverse reactions by personalizing the CAR T-cell dosing,
- Use of new, substantially improved forms of CAR T-cell targeting multiple B cell antigens,
- The possibility of treating the patients that relapsed following the CD-19 CAR T-cell treatment,
- Wider-range of B-cell malignancies that could be treated,
- The use of CAR T-cell and other cell-based cancer immunotherapy forms for the treatment of hematological and solid tumors, and
- Scientific and technological development.
