Published on April 23rd, 2013 | by Michael Ricciardi
Cancer Therapy News: Radioactive Microbes, Altered Immune Cells Succeed As Anti-Cancer Treatments
Two recent successes in cancer treatment (metastatic pancreatic cancer, acute lymphoblastic leukemia) are reported here.
Researchers Use Weakened Bacteria to Deliver Radiation Directly to Cancer Cells
The bacterium Listeria monocytogenes is a rod-shaped bacterium that can by-pass a cell’s defenses and penetrate its interior, potentially causing severe diseases such as meningitis. In healthy people (those without compromised immune systems), the microbe is usually eliminated by immune cells before any significant damage is done. This ability to penetrate cells — especially immune cells called macrophages — was exploited by researchers to target cancer cells and destroy them.
Using an “attenuated” or weakened strain of the bacteria with small segments of tumor DNA attached to them to infect tumor cells, researchers (Gravekamp et al) were able to “teach” other immune cells to recognize and destroy the tumor cells before they could metastasize (spread to other tissue). Surprisingly, the modified microbes did not simply trigger the desired immune response — they actually invaded the tumor cells and killed them directly.
Using this established technique, a team of researchers at Albert Einstein School of Medicine in New York City (Quispe-Tintaya et al) combined the attenuated microbe with a radio isotope called rhenium-188 via an engineered monoclonal antibody (a highly specialized protein) that attaches and sticks to the Listeria bacterium.
Mice that were already infected with a metastatic form of pancreatic cancer (one of the most lethal forms of cancer due to its ability to rapidly spread to other tissue) were injected with the engineered radioactive Listeria (RL). After a 16 day period, results were impressive: a 90% reduction in the number of metastatic cells compared to a control group (who received a saline solution).
Remarkably, the weakened Listeria without the radioactive “label” were able to clear 50% of the metastatic cells although the their impact on the original tumor cell was less dramatic (but still significant). Normal (non-weakened) Listeria was able to shrink the tumor by 20%. The combination of the attenuated bacterium and the radionuclide label was able to shrink the tumor by 64%.
Although 90% clearance by RL is laudable, the remaining 10% of metastatic cells can still spread cancer. The researchers hope to achieve 100% clearance by using a longer lasting radionuclide label.
Also significantly: the treatment mostly spared healthy cells in the surrounding tissue, causing little detectable damage. The technique work primarily because it exploits a trick cancer cells use to avoid being destroyed by the immune system; many cancer cells release small proteins called cytokines that tell immune cells “nothing to see here, move along.” They also recruit other immune-suppressing cells to insure their survival.
In a press statement, lead investigator Claudia Gravekamp explained:
“By turning off the immune cells that would have protected them, the cancer cells make themselves uniquely vulnerable to the treatment. We envision this approach as a second-line therapy, which would follow either surgery or radiation to remove the primary tumor.”
This success represents the first improvement in pancreatic cancer treatment in 25 years.
The research was reported today on-line in the Proceedings of the National Academy of Sciences under the title: ‘Nontoxic radioactive Listeriaat is a highly effective therapy against metastatic pancreatic cancer’
Engineered Immune Cells Rapidly Clear Bone Tumors in Leukemia Patients
It was a small experiment — just five patients suffering from acute lymphoblastic leukemia received the altered immune cell treatment — but the results in four of the five patients tested have surprised even the doctors conducting the trial.
Leukemia is an auto-immune cancer in which key immune cells turn against healthy cells (as though they were pathogens) and destroy them. This particular disease is a fast-progressing form of Leukemia that kills 60% of those with the condition.
The treatment — once thought of a “fringe” treatment — involves extracting a type of immune cell called T lymphocytes (or T cells), altering them to over-express a receptor* for a small protein found on a different immune cell type called B Lymphocytes (B cells). This prompts the T cells to attack the B cells. B cells are found in both healthy and cancerous cell tissues. The T cells have no way of discriminating between the healthy and tumorogenic type, and so, attack and kill all of them.
“All of our patients very rapidly cleared the tumor. [The treatment] worked much faster than we thought” said says Michel Sadelain, a researcher at the Memorial Sloan-Kettering Cancer Center in New York and an author of the study. [source]
Variations of this type of immunotherapy have been around for at least five or six years and have shown promising results against a variety of cancers. However, many researchers have remained incompletely convinced. These newest results (though from a small sample size) may help convince the skeptics, or at least prompt more research on larger patient populations.
* second-generation dual-signaling chimeric antigen receptor (CAR) termed 19-28z.
Results of the trialusing five patients with acute lymphoblastic leukemia were published in Science Translational Medicine under the title: ‘CD19-Targeted T Cells Rapidly Induce Molecular Remissions in Adults with Chemotherapy-Refractory Acute Lymphoblastic Leukemia‘ (Brentjens et al)
Source material for this last news item came from the Scientific American article ‘Genetically Engineered Immune Cells Found to Rapidly Clear Leukemia Tumors’ by Heidi Ledford and Nature magazine (first published on March 20, 2013).