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30 years later, IMAK Method featured in a major medical journal

June 25, 2023
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After more than three decades of work, Prof. Slavin and the Biotherapy International team have presented the results of one of their most innovative methods – the use of intentionally-mismatched donor lymphocytes activated prior to administration for anti-cancer immunotherapy. The full report appeared in April’s edition of the Journal of Cancer Research and Clinical Oncology, one of the most prestigious publications on anti-cancer research.

What did this study address?

Currently, there are few treatments available for patients with hematologic malignancies (also known as blood cancers) who do not respond well to conventional chemotherapy drugs. Within the immunotherapy niche, these patients are occasionally treated using a stem cell transplant (SCT), alongside high-dose chemotherapy – with or without whole-body radiation. This is then followed by administering bone marrow-derived stem cells, obtained either from a fully-matched family member or matched unrelated donor.

This treatment can initiate a good immune response by donor lymphocytes that will sometimes induce a successful fight against residual malignant cells. However, an SCT also carries major procedure-related risks: it can interact with high-dose chemotherapy, and it may trigger a condition known as graft-vs-host disease (GVHD). This is a potentially hazardous reaction where the donor lymphocytes also attack a patient’s normal tissues including skin, liver, and gastro-intestinal system. 

Severe GVHD resulting soon after SCT is known as acute GVHD. However, GVHD can also appear much later after the transplant, which is known as Chronic GVHD. This can severely impair a patient’s quality of life and may need continuous drug treatment to suppress the attack caused by the permanent circulation of the donor’s immune system cells following the engraftment of the donor’s stem cells. Currently, the available immunosuppressive medications can help with acute and chronic GVHD, but the failure to prevent and treat established GVHD  may be deadly. Unfortunately, despite the positive anti-cancer effects induced by donor lymphocytes, the unavoidable recurrent disease continues to represent a major cause of transplant failure.

At Biotherapy International, Prof. Slavin’s team is continuously pushing the development of safer and more effective innovative cell-mediated immunotherapy for the cure of cancer, both hematologic malignancies and metastatic solid tumors. Following successful preclinical studies in animal models of human diseases, they designed a new method that could offer a higher success rate and lower complications.

About the new immunotherapy protocol for the treatment of cancer with cure potential

The recently published study reports the outcomes of 33 patients treated with Intentionally Mismatched pre-treatment Activated Killer cells (IMAK). All patients were diagnosed with a multi-drug resistant form of cancer, such as acute myeloid leukemia (AML) acute lymphoblastic leukemia, non-Hodgkin’s lymphoma, and multiple myeloma. 

All these patients had already received conventional chemotherapy or even high-dose hematopoietic stem cell transplantation and relapsed with progressive disease. Consenting patients with multi-drug resistant cancer cells, who had failed to respond to all available anti-cancer modalities, are considered incurable. This justifies experimental therapeutic approaches on a fully compassionate basis.

Accordingly, Prof. Slavin used intentionally-mismatched infusions, containing interleukin 2 (IL-2) activated blood lymphocytes obtained from a family member or unrelated volunteers. Activation of lymphocytes results in 3 types of cancer-killer cells: T cells, natural killer (NK) cells, and also NKT cells. 

Such pre-activated killer cells can kill every foreign cancer cell, regardless of their resistance to chemotherapy, within minutes or a few hours. Instead of using SCT (Stem cell transplantation) with genetically matched donor lymphocytes, which are not as effective in rejecting genetically compatible cancer cells following successful SCT, Slavin preferred only short-term circulation of much more effective mismatched cancer-killing lymphocytes. These cells don’t need SCT, since such cells could trigger a more powerful, but short-lived immune reaction that could combat malignant cells much faster.

This method turned out to be most successful based on two accounts: first, by producing a stronger and faster reaction against cancer cells; second due to consistent rejection of all mismatched lymphocytes within less than a weak, in addition to achieving faster results, elimination of donor killer cells prevented the development of GVHD. Out of the original 33 patients reported, only 6 continued with progressive disease while 22 of them had a good complete response or went into long-lasting remission and cure. For example, the first patient to receive this treatment has now been in remission for 30 years and counting – you can read her full story here.

Interestingly, by avoiding a stem cell transplant altogether, none of these patients developed GVHD and most of the patients presented with only mild to moderate side effects, such as skin erythema (reddening), short-term fever or chills, or a temporary reduction in their red and white blood cell levels. None of them needed to be hospitalized due to these adverse reactions.

The results in simple terms: Promising

At first glance, 33 patients may not seem like a lot. However, prof. Slavin’s study did not deal with the mass deployment of a new pharmaceutical product. Instead, it dealt with people who were considered otherwise incurable, and who had largely been deemed terminal by the medical establishment.

For 22 of them, the technique of intentionally mismatched donor cells has already proved invaluable. For one 12-year-old girl, it already gave her access to a life she may have missed otherwise. Overall, it seems that 6 of the 22 patients that maintained disease-free status for more than 5 years with no further treatment should be considered cured.

And for the advancement of oncology? The study – which you can read fully here – shows three important things: that this new treatment is feasible, safer than many alternatives, and most effective with cure potential especially if applied against a relatively low number of residual multi-drug resistant cancer cells.

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