KRN-7000 liposomal

Nano-sized membrane bubbles known as extracellular vesicles activate the immune system in mice and seem to render their tumors sensitive to a type of immunotherapy drug called a checkpoint inhibitor. Nano-sized membrane bubbles known as extracellular vesicles activate the immune system in mice and seem to render their tumours sensitive to a type of immunotherapy drug called a checkpoint inhibitor. This is according to a new study published in Cancer Immunology Research by researchers at Karolinska Institutet in Sweden. Treatments for various forms of cancer have improved considerably over recent years thanks to a type of drug called a checkpoint inhibitor, which helps the immune system's T cells to attack the cancer cells. However, even though some patients respond extremely well to treatment, a large proportion only see temporary improvement, if any. Scientists are devoting considerable energy to understanding why this is so and to combining checkpoint inhibitors with other therapies in order to increase the cancer survival rate. A new cancer therapy Researchers from Karolinska Institutet how show that a form of round nanoparticles called exosomes or extracellular vesicles are a promising path to follow. "Is seems that the vesicles make the tumour immunologically active so that the checkpoint therapy can gain purchase and start to work," says the study's last author Susanne Gabrielsson, professor at the Department of Medicine (Solna), Karolinska Institutet. "These results give support to the further development of extracellular vesicles as a new cancer therapy." Extracellular vesicles are sometimes referred to as the body's messengers. They are membrane-bound nano-scale bubbles that cells can send to each other to exchange information. Vesicles from tumour cells, for instance, can switch off the immune system so that the cancer can spread, while vesicles from immune cells can activate an immune response. Can activate immune cells In earlier studies, the KI researchers have shown that a certain type of extracellular vesicle from immune cells can activate immune T cells and reduce tumour growth in mice. In the present study, they examined how these vesicles function in a mouse model of a skin cancer that is resistant to checkpoint inhibitor therapy. The extracellular vesicles used in the study were isolated from the mice's own immune cells (dendritic cells). An in this case cancer-specific protein called ovalbumin and a molecule called alpha-Galactosylceramide were then added, both of which stimulate T cells and natural killer cells. When the vesicles were introduced into mice therapeutically to treat their tumours or prophylactically before their tumours had started to develop, they activated their immune systems to produce a strong T-cell response to the cancer protein. The same effect was not achieved if the animals were only given checkpoint inhibitors, and was most pronounced in animals that received a combination of vesicles and checkpoint therapy. However, the researchers observed no effect on survival when the animals received the vesicle-checkpoint combination therapy compared with vesicles alone, and believe that the duration of the experiment was possibly too short for the activated immune system to affect the tumours. When the treatments were given prophylactically to mice, which gives a longer duration of action, the mice that received the combination treatment showed greater survival than those that only received vesicles. Tested on human patients Other researchers tried giving extracellular vesicles from immune cells to human patients as a cancer therapy already back in 2005. In these studies, the vesicles have proved safe but only minimally effective. Professor Gabrielsson believes that this was because the experiments were conducted too early, before scientists knew what molecules the vesicles should contain to be effective, something to which her team has devoted considerable effort. They are also trying to simplify the manufacture of the extracellular vesicles. "Our aim is to be able to use cell lines instead of having to take the patients' own cells," she says. "This will mean that the vesicles can be prepared in advance and frozen until needed. We also believe that variants of the treatment could be used for other forms of cancer and other diseases." The study was supported by grants from the Swedish Research Council, the Swedish Cancer Society, the Cancer Research Funds of Radiumhemmet, Region Stockholm and the Swedish Heart-Lung Foundation and with KID funding from Karolinska Institutet. Susanne Gabrielsson holds a patent for immunotherapeutic exosomes from B cells and is on the scientific advisory committee at Anjarium Biosciences.

Earlier studies have shown that a single dose of RGI-2001 given on the day of transplant was safe and potentially contributed to preventing acute graft-versus-host disease. REGiMMUNE’s lead candidate to prevent graft-versus-host disease after stem cell transplants has passed its phase 2 trial, setting the Taiwan-based biotech up for a late-stage test. The therapy, dubbed RGI-2001, is designed to activate regulatory T cells through a novel mechanism that the company claimed could also have applications for the treatment of other autoimmune and chronic inflammatory diseases. The study assessed 47 patients across the U.S. who received six weekly doses of RGI-2001—as well as standard immunosuppression in the form of Prograf and methotrexate—following allogeneic hematopoietic cell transplantation. Between 20% and 40% of patients who undergo this form of transplant develop clinically significant acute graft-versus-host disease (aGvHD). The disease is a reaction of donor immune cells against host tissues that is associated with significant morbidity and death. The results, which the company presented at the American Society of Hematology annual meeting earlier in the month, showed that there were no cases of engraftment failure and no serious adverse events attributed to RGI-2001. In the first 100 days, 20% of patients experienced aGvHD of grades II to IV, although only two of these cases were grade III or IV severity, the company noted. By Day 180, almost 94% of participants had survived, with 75% having avoided aGvHD of grades II to IV and just 4% experiencing disease relapse. RGI-2001 contains the active moiety α-GalCer encapsulated in a liposomal glycolipid. This is designed to bind to the CD1d receptor of antigen-presenting cells resulting in activation of invariant natural killer cells, ultimately modulating the GVHD pathogenic cascade. Earlier studies have shown that a single dose of RGI-2001 given on the day of transplant was safe and potentially contributed to preventing aGVHD. The company touted the latest results as “compelling,” adding that the biotech is “strongly considering moving forward with a phase 3 study.” “We are definitely encouraged by the positive results from this study; it also provides a strong foundation to confidently advance our plans for phase 3 study,” REGiMMUNE CEO Kenzo Kosuda said in a statement Dec. 20. There are already a few drugs on the market for various severities of GvHD disease. Last year, Kadmon—since acquired by Sanofi —nabbed an FDA approval for its first-in-class ROCK2 inhibitor Rezurock for a chronic form of GVHD. It joined Johnson & Johnson and AbbVie’s BTK inhibitor Imbruvica as well as Incyte’s Jakafi. The most recent regulatory development was almost exactly a year ago, when Bristol Myers Squibb's long-standing rheumatoid arthritis drug Orencia was granted another lease on life after an FDA approval for aGVHD.