Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from a somatic cell. Pluripotent stem cells hold promise in the field of regenerative medicine. Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic, and liver cells), they represent a single source of cells that could be used to replace those lost to damage or disease.

Natural killer cells are the type of cytotoxic lymphocyte critical to the innate immune system. The role NK cells play is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cells, acting at around three days after infection, and respond to tumor formation. 

Typically, immune cells detect the major histocompatibility complex (MHC) presented on infected cell surfaces, triggering cytokine release, causing apoptosis. NK cells are unique, however, as they can recognize stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction.

Clinical Trial on NK cells

In a first clinical trial, a natural killer cell immunotherapy derived from induced pluripotent stem cells is being tested for safety in 64 patients with a variety of solid tumors. The first subjects used for the study received the cells in February at the University of California, San Diego (UCSD) Moores Cancer Center and MD Anderson Cancer Center. 

This study is targeting late-stage cancer patients with solid tumors, including lymphoma, colorectal cancer, and breast cancer. The FT500 NK cells do not undergo any further alterations and after their derivation from the induced pluripotent stem cells (iPSCs), offering the possibility of a quicker, ready-made treatment. 

Human embryonic stem cells induced iPSCs 

Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) provide an accessible, genetically tractable, and homogenous starting cell population to efficiently study human blood cell development. These cell populations provide platforms to develop new cell-based therapies to treat both malignant and nonmalignant hematological diseases.

The NK cells are immune cells in the same family as T and B cells and are very good at targeting cancer cells for destruction. Some Laboratory experiments have shown they do so by attacking cells that have lost their significant self-recognition signals that tell the immune system not to attack. This is the phenomenon that can happen among cancer cells but not to healthy cells. Experts are not sure how many cancer cells lose that signal. Researchers are hopeful that the clinical trial can help determine which cancer patients could benefit the most from NK cell treatment. 

iPS Clone

The ability to induce pluripotent stem cells from committed, human somatic cells provides tremendous potential for regenerative medicine. However, there is a defined neoplastic potential inherent to such reprogramming that must be understood and may offer a model for critical understanding events in the formation of the tumor. Using genome-wide assays, we identify cancer-related epigenetic abnormalities that arise early during reprogramming and persist in induced pluripotent stem cell (iPS) clones. These include hundreds of abnormal gene silencing events, patterns of aberrant responses to epigenetic-modifying drugs resembling those for cancer cells, and presence in iPS and partially reprogrammed cells of cancer-specific gene promoter DNA methylation alterations.

Progress in adoptive T-cell therapy for cancer and infectious diseases is hampered by the lack of readily available antigen-specific, human T lymphocytes. Pluripotent stem cells could provide an estimable source of T lymphocytes, but the therapeutic potential of human pluripotent stem cell-derived lymphoid cells generated to date remains uncertain.

Modification of T cells

Recently, some Approved cell therapies for Cancer also rely on modifying T cells, in those cases to produce cancer cell–binding chimeric antigen receptors (CARs), and have been effective in treating certain cancers such as leukemia.

Application of CAR T-Cell Therapy in Solid tumours

The Car T technology has wowed the field by all but obliterating some patients’ blood cancers, but solid malignancies present new challenges.

Therapies that contains such chimeric antigen receptor (CAR) T cells have been approved for some types of so-called liquid cancers of the blood and bone marrow, large B-cell lymphoma and B-cell acute lymphoblastic leukemia. But the approach has not had as much success for solid tumors.

Serious research into the therapy for brain cancer started almost 20 years ago after cancer biologist WaldemarDebinski, then at Penn State, discovered that the receptor for the immune signaling molecule interleukin 13 (IL-13) was present on glioblastomas, but not on healthy brain tissue. The receptor thus seemed like an excellent target to home in on cancer cells while sparing healthy ones. The CAR spacer domain that spans the immune cells’ membranes and its intracellular co-stimulatory areas, as well as the process used to expand cells outside the body, to boost the T cells’ activity.

CAR T- A Safer Cell Therapy

While managing CAR T-cell therapy toxicity could help keep already-designed treatments on their march to the clinic, many immunotherapy companies are also working to develop a new generation of inherently safer therapies, yet just as efficient. A crucial part of achieving this goal will be improving CAR specificity for target cells. With current treatments, the destruction of normal cells is often an unavoidable side effect when healthy tissue carries the same antigens as tumors; noncancerous B cells, for example, are usually casualties in CD19-targeted therapies.

CAR T delivery is a non-easy factor in the treatment of solid tumors and other unknown forms of tumors. With the non-solid cancers, cells are administered by a blood infusion, and once in circulation, the CAR T can seek out and destroy the rogue cells. For solid tumors, it’s not so simple.

The main drawback of taking cells from a patient and developing them into a cellular immunotherapy product is that the process can take weeks. 

Patel tells The Scientist “But for the majority of patients who may not be a candidate or may not have time to wait for such an approach, the idea that there’s off-the-shelf immunotherapy that could potentially as a living drug act against their cancer, I think is a fascinating concept,”  

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