IMPROVING ON CAR IMMUNOTHERAPY APPROACH
When we stated that chimeric antigen receptor CAR immunotherapy process was created to remain and improve, we aimed at demonstrating our conviction that the CAR approach will eventually be improved and become the gold standard for the treatment of many cancers. We observed that many research and medical institutions are using all advanced information, state-of-the-art techniques and technologies in order to get rid of the concerning serious adverse events caused by the CAR T approach, in addition to boosting its capability to treating solid tumors not only blood and lymph cancers.
Recently, we witnessed serious efforts towards improving the CAR T approach. As a matter of fact, we witnessed an FDA assigned advisory committee granting a BIG YES for the approval of Novartis CAR-T immunotherapy product CTL019 for pediatric acute lymphoblastic leukemia. We also expect another recommendation for the approval of Kite Pharma’s (KITE) CAR T- Cell product for aggressive B-cell non-Hodgkin lymphoma.
The CAR T-cell is Not the Only CAR Immunotherapy Approach
NATURAL KILLER Cells Are Replacing the Immune System T CELLS
Indeed, instead of genetically engineering the immune system’s T–cells as therapy for cancer, a chimeric antigen receptor (CAR) has been created with Natural killer cells. A Company called Nantkwest (NK) is developing CAR NK therapy approach. This firm is showing the advantages of using NK cells instead of T Cells as a therapy approach for cancer. We will deal with this firm at length in another article.
As for the current news about CAR NK immunotherapy, a top grade distinguished cancer institution, MD Anderson Cancer Center has come up with a procedure, the CAR cord blood-derived NK-Cells that seem to be free of the problems, which the T Cell approach still endures.
In The NEWS
MD Anderson Cancer Center’s researchers reported preclinical results in the Journal Leukemia demonstrating that cord blood natural killer (NK) cells derived from donated umbilical cords can be modified to seek and destroy some types of cancers.
Using a viral vector, the researchers transduce NK cells taken from cord blood with the CD19 CAR, IL-15 gene, and an inducible caspase-9-based suicide gene.
Inducing CD19 CAR NK from cord blood turn the CAR NK into a guided missile.
Inducing IL-15 gene enabled the NK cells to stay in the body long enough in order to seek, find and kill cancer cells.
Inducing a suicide gene allows the modified cord blood NK cells to be shut down in case a severe inflammatory response such as the cytokine release syndrome (CRS) occurs.
One of the worst CAR T- CELL treatments’ side effects is CRS, which caused many hospitalizations and is life-threatening.
MD Anderson researchers have also demonstrated that modified cord blood NK cells do not cause the immunological reaction known as graft versus host diseases (GVHD), which causes severe symptoms that affect the skin and various other body systems, in addition to being life-threatening.
This means that the CAR NK product could be available off-the-shelf.
Some Results and Insight
– In cell lines and mouse models of cancers lymphoma and chronic lymphocytic leukemia (CLL), CD19-targeted cord blood NK cells killed the malignant cells and extended survival of animals compared to simply giving NK cells alone.
– An experiment showed the engineered NK cells from cord blood killed chronic lymphocytic leukemia CLL cancer cells much more efficiently than NK cells taken from CLL patients. This result highlights the need to transplant CAR-engineered NK cells from healthy cord blood rather than use a patient’s own cells.
– Mouse model lymphoma experiments using a single infusion of low dose NK cells resulted in prolongation of survival. At a higher, double dose, NONE of the mice treated with the CD19/IL-15 cord blood NK cells died of lymphoma, with half surviving for 100 days and beyond. All mice treated with other NK cells died by day 41.
According to MD Anderson, a first-in-human Phase I/II clinical trial of the cord-blood-derived, chimeric antigen receptor-equipped natural killer cells started at MD Anderson in June for patients with relapsed or resistant chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), or non-Hodgkin lymphoma.
The question is which one of the immunooncology developing firms would be awarded the right for MD Anderson’s CAR NK approach. Will this famous medical center create a new firm to conduct further trials and continue developing the product until approval?
Another important question is: Could the obvious success of the developed cord blood-derived natural killer CAR impact in anyway Nantkwest’s (NK) CAR NK products?
Let’s first have a look at,
Nantkwest is a clinical-stage company using the natural killer (NK) cells to treat cancer, infectious diseases and inflammatory diseases. Natural Killer cells are ancient cells in the human body designed to recognize and detect cells under stress or infected. Nantkwest’s “off-the-shelf” activated Natural Killer (NK) platform may have the capacity to destroy cancer and virally infected cells from the body.
Nantkwest tested the safety of NK cells as well as their activity against a broad range of cancers in multiple phase 1 clinical trials in the United States, Canada and Europe. In addition to its NK cells’ capability to be administered in the outpatient setting as an “off-the-shelf” living drug. The therapy has no need for individualized patient matching.
Nantkwest’s NK cell based platform has been bioengineered to incorporate chimeric antigen receptors (CARs) and antibody receptors to further optimize targeting and potency in the therapeutic disease.
So, what difference does exist between MD Anderson’s CAR NK immunotherapy and Nant-kwest’s CAR NK immunotherapy?
There are differences, including the fact that MD Anderson’s source of NK cells is the cord blood, which the famous medical center considers a primary reason for the safety and efficacy of its product. Yet, a lot has to be considered including some testing results and other important facts from and others.
We will deal with this topic in the article about the CAR T and CAR NK that will be one of the main topics in the upcoming Prohost Letter #412 to be published among other important news and facts revealed by Nantkwest.
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Important Positive News
Nektar Therapeutics (NKTR) announced positive topline results from an oral Human Abuse Potential (HAP) study of the firm’s product NKTR-181 – a first-in-class opioid analgesic.
NKTR-181 is a new chemical entity (NCE) that is the first full mu-opioid agonist molecule designed to provide potent pain relief without the high levels of euphoria that can lead to abuse and addiction with standard opioids.
NKTR-181 is the first analgesic opioid molecule to exhibit reduction in specific CNS-mediated side effects, like euphoria, through the strategic alteration of brain-entry kinetics. The product has been granted the Food and Drug Administration’s (FDA) Fast Track designation for moderate to severe chronic pain.
The NKTR-181 HAP study was designed to confirm and assess the relative oral abuse potential of NKTR-181 at its maximum analgesic or therapeutic dose (400 mg) and at a supratherapeutic dose (3 times to 12 times greater than its analgesic dose range of 100 mg to 400 mg) compared to common therapeutic doses of a Schedule II opioid, oxycodone.
NKTR-181’s less rewarding properties and strong analgesia are inherent to its novel molecular structure and independent of any abuse-deterrent formulation. Many patients do not receive adequate pain relief because they fear taking conventional opioids, including abuse-deterrent formulations, because of their potential for abuse and addiction.
We believe NKTR-181 could be a fundamental building block in the fight against prescription opioid abuse. Nektar is committed to bringing this new pain treatment to patients and physicians as quickly as possible
In March 2017, NKTR-181 completed a Phase 3 efficacy trial (SUMMIT-07) in 610 patients with moderate to severe chronic low back pain who were new to opioid therapy (opioid-naïve). SUMMIT-07 evaluated four analgesic doses of NKTR-181 (100 mg, 200 mg, 300 mg and 400 mg). Patients in the trial achieved an average pain score reduction of over 65% (from 6.73 at screening to 2.32 at randomization) during the dose titration period.
The primary efficacy endpoint of the study demonstrated significantly improved chronic back pain relief with NKTR-181 compared to placebo (p=0.0019). Key secondary endpoints of the study also achieved high statistical significance. The study demonstrated that NKTR-181 had a favorable safety profile and was well tolerated.
Any news that emerges about a product that can stop diminish the number of addicts in people who need pain killers is great news. Addictive painkillers stop pains but cause craving of the addictive drugs, which destroy human bodies and souls and families and can become life-threatening. The problem is huge and any successful attempt to create potent, non-addictive pain killers could save many lives. We believe Nektar’s pain killer drug NKTR-181 will be the one. The reason for our optimism is that Nektar Therapeutics is polymer chemistry giant. The firm has a powerful approach to drug design and to the creation of new molecular entity drugs with optimized pharmacology.
Nektar’s successful products are derived from two key strategies:
- Targeting well-characterized bio-molecular pathways considered likely to yield significant therapeutic benefits.
- the firm’s exploitation of the structural malleability of polymers — key chemical building blocks that provide a near-limitless toolbox with which to customize the behavior of a new molecule.
Nektar’s methodology has led to an inspiring number of approved medicines that are treating people around the world.
Extremely important, game changing news has recently come through Nektar’s superior chemistry accomplishment. We will also write about it in the upcoming Prohost Letter #412.
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