Category Archives: Cell Therapy

Meet the new medicines, page 5

In CAR-T cell therapy, immune cells are removed from a patient, genetically modified, then put back into the patient to fight against cancer. This approach has met with substantial success against blood cancers. For example, one CAR-T cell therapy, approved in August 2017, is now being used to treat children with acute lymphoblastic leukemia.

In cell transplants, patients are given functional cells as a replacement. When patients with blood cancers undergo chemotherapy, their blood stem cells get destroyed. Afterward, they receive a transplant of blood stem cells collected either from themselves before chemotherapy or from a separate donor so that they can continue to make blood.

Examples of cell replacement therapies that are in the early stages of clinical study include:

A different type of cell therapy takes advantage of certain cell properties to deliver drugs. For example, cancer cells have a self-homing ability, moving around the body to find tumors and spread. An HSCI scientist has co-opted this ability, using cancer cells to deliver tumor-killing proteins.

Another example is mesenchymal stem cells, which are attracted by inflammation and can home to a site of injury. They can be used to deliver small-molecule or biologic drugs.

Many cell therapies that have reached the stage of clinical trials are bespoke to each patient. Because the cells come from patients themselves, this is referred to as autologous.

Because of this, manufacturing is never done in bulk quantities just one batch per patient. This process needs to be highly controlled and accurate, and the success rate extraordinarily high for a very small number of patients. However, it is currently a very expensive process, in part because each product made is the full run.

Other types of cell therapies make use of cells from another person, and are called allogeneic. The manufacturing and regulatory advantage is having a product that can cover many people. But the medical risk is that the cells will be identified as foreign and rejected by the immune system in the absence of a way to protect the them from the immune attack.

HSCI scientists are working on a couple of ways to create cell therapies that would not be rejected by the immune system:

If cell therapy is ever going to be available to large numbers of people, we will need disruptive breakthroughs in academic, commercial, and industrial research and development.

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Cell therapies | Harvard Stem Cell Institute (HSCI)

SAN DIEGO, April 13, 2023 (GLOBE NEWSWIRE) -- Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, today announced that two key industry opinion leaders and management will participate in Oppenheimer & Co.’s Virtual Fireside Chat: Discussion of ROR1 CAR-T Cell Therapy in Hematological Malignancies and Solid Tumors on Tuesday, April 18, 2023 at 1:30 p.m. EDT.

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Oncternal Therapeutics Participating in Oppenheimer & Co.’s Virtual Fireside Chat: Discussion of ROR1 CAR T Cell Therapy in Hematological...

Approved oral medications

Two oral medications are FDA-approved for treating adults with very rare cases of advanced BCC that are large or have penetrated the skin deeply, spread to other parts of the body or resisted multiple treatments and recurred.

Vismodegib (Erivedge)Sonidegib (Odomzo)

Both medications are targeted drugs taken by mouth. They work by blocking the hedgehog signaling pathway, a key factor in the development of BCC. In 2012, vismodegib became the first medicine ever approved by the FDA for treating advanced BCC. A second hedgehog pathway inhibitor (HHI) drug, sonidegib, was approved for advanced BCC in 2015.

Vismodegib is used for the extraordinarily rare cases of metastatic BCC or locally advanced BCC (tumors that have penetrated the skin deeply or frequently recurred) that either recur after surgery or radiation, or cannot be treated with surgery or radiation and have become dangerous or life-threatening.

Sonidegib is used in adults with BCC that is locally advanced, penetrating the skin deeply or repeatedly recurring, as well as in cases when other treatments such as surgery or radiation cannot be used.

Due to a risk of birth defects, women who are pregnant or may become pregnant should not use either drug. Couples must use birth control if the woman is capable of becoming pregnant while her partner is taking the medication.

Scientists are also investigating several other targeted hedgehog inhibitors as potential treatments for locally advanced and metastatic BCC.

In February 2021, the U.S. Food and Drug Administration (FDA) approved the intravenous immunotherapy medication,cemiplimab-rwlc(Libtayo) for treating patients with certain forms of advanced basal cell carcinoma.

Cemiplimab-rwlc(Libtayo)

Cemiplimabis a type of immunotherapy known as a checkpoint blockade therapy, which works by harnessing the power of the immune system to battle cancer. Under normal conditions, the immune system uses checkpoints, which are molecules that suppress production of T cells, the white blood cells that help protect the body from infection. These checkpoints keep T cells from overproducing and attacking normal cells in the body. However, cancer cells have the ability to keep those checkpoints active, suppressing the immune system so the cancer can grow and thrive. Cemiplimabblocks a particular checkpoint called PD-1 from working, so the immune system can releasemassive amounts of T cells to attack and kill cancer cells.

Find out more aboutcemiplimab.

Cemiplimabis used to treat patients with advanced basal cell carcinoma (BCC) previously treated with a hedgehog pathway inhibitor (HHI) or for whom an HHI is not appropriate. Full approval was granted for patients with locally advanced BCC and accelerated approval was granted for patients with metastatic BCC.

Link:
Basal Cell Carcinoma Treatment - The Skin Cancer Foundation

How Cellular Immunotherapies Are Changing the Outlook for Cancer Patients

Reviewed By:

Philip D. Greenberg, MD.Fred Hutchinson Cancer Research Center

Some of these approaches involve directly isolating our own immune cells and simply expanding their numbers, whereas others involve genetically engineering our immune cells (via gene therapy) to enhance their cancer-fighting capabilities.

Our immune system is capable of recognizing and eliminating cells that have become infected or damaged as well as those that have become cancerous. In the case of cancer, immune cells known as killer T cells are particularly powerful against cancer, due to their ability to bind to markers known as antigens on the surface of cancer cells. Cellular immunotherapies take advantage of this natural ability and can be deployed in different ways:

Today, cell therapies are constantly evolving and improving and providing new options to cancer patients. Cell therapies are currently being evaluated, both alone and in combination with other treatments, in a variety of cancer types in clinical trials.

Cancer patients have naturally occurring T cells that are often capable of targeting their cancer cells. These T cells are some of the most powerful immune cells in our body, and come in several types. The killer T cells, especially, are capable of recognizing and eliminating cancer cells in a very precise way.

The existence of these T cells alone, however, isnt always enough to guarantee that they will be able to carry out their mission to eliminate tumors. One potential roadblock is that these T cells must first become activated before they can effectively kill cancer cells, and then they must be able to maintain that activity for a sufficiently long time to sustain an effective anti-tumor response. Another is that these T cells might not exist in sufficient numbers.

One form of adoptive cell therapy that attempts to address these issues is called tumor-infiltrating lymphocyte (TIL) therapy. This approach harvests naturally occurring T cells that have already infiltrated patients tumors, and then activates and expands them. Then, large numbers of these activated T cells are re-infused into patients, where they can then seek out and destroy tumors.

Unfortunately, not all patients have T cells that have already recognized their tumors. Others patients might, but for a number of reasons, these T cells may not be capable of being activated and expanded to sufficient numbers to enable rejection of their tumors. For these patients, doctors may employ an approach known as engineered T cell receptor (TCR) therapy.

This approach also involves taking T cells from patients, but instead of just activating and expanding the available anti-tumor T cells, the T cells can also be equipped with a new T cell receptor that enables them to target specific cancer antigens. By allowing doctors to choose an optimal target for each patients tumor and distinct types of T cell to engineer, the treatment can be further personalized to individuals and, ideally, provide patients with greater hope for relief.

The previously mentioned TIL and TCR therapies can only target and eliminate cancer cells that present their antigens in a certain context (when the antigens are bound by the major histocompatibility complex, or MHC).

Recent advances in cell-based immunotherapy have enabled doctors to overcome this limitation. Scientists equip a patients T cells with a synthetic receptor known as a CAR, which stands for chimeric antigen receptor.

A key advantage of CARs is their ability to bind to cancer cells even if their antigens arent presented on the surface via MHC, which can render more cancer cells vulnerable to their attacks. However, CAR T cells can only recognize antigens that themselves are naturally expressed on the cell surface, so the range of potential antigen targets is smaller than with TCRs. In October 2017, the U.S. Food and Drug Administration (FDA) approved the first CAR T cell therapy to treat adults with certain types of large B-cell lymphoma.

Given their power, CARs are being explored in a variety of strategies for many cancer types. One approach currently in clinical trials is using stem cells to create a limitless source of off-the-shelf CAR T cells. This may have application to only selected settings, but could allow doctors to treat patients in a timelier fashion.

More recently, adoptive cell therapy strategies have begun to incorporate other immune cells, such as Natural Killer (NK) cells. One application being explored in the clinic involves equipping these NK cells with cancer-targeting CARs.

There are currently two adoptive cell therapies that are approved by the FDA for the treatment of cancer.

Side effects may vary according to the type of adoptive cell immunotherapyand what exactly it targetsand may also be influenced by the location and type of cancer as well as a patients overall health. Potential cell therapy-related side effects often take the form of an overactive immune response and may lead to excessive inflammation via cytokine release syndrome (also known as cytokine storm), and also to neurotoxicity from inflammation in the brain. Side effects can range from mild to moderate and may become potentially life-threatening under certain circumstances.

Fortunately, in most cases, potential immunotherapy-related side effects can be managed safely as long as the potential side effects are recognized and addressed early. Therefore, its extremely important that patients inform their medical care team as soon as possible if they experience any unusual symptoms during or after treatment with cancer immunotherapy. In addition, patients should always consult their doctors and the rest of their care team to gain a better and fuller understanding of the potential risks and side effects associated with specific adoptive cell immunotherapies.

Common side effects associated with currently approved adoptive cell therapies may include but are not limited to: acute kidney injury, bleeding episodes, heart arrhythmias, chills, constipation, cough, cytokine release syndrome (cytokine storm), decreased appetite, delirium, diarrhea, dizziness, edema, encephalopathy, fatigue, febrile neutropenia, fever, headache, hypogammaglobulinemia, hypotension, hypoxia, infections, nausea, neurotoxicity, pyrexia, tachycardia, tremors, and vomiting.

Throughout its history, CRI has supported a variety of basic research projects aimed at improving our understanding of the identity and functions of our many immune cells as well as translational and clinical efforts that seek to use these insights in the development of cellular immunotherapies for cancer patients in the clinic.

Some of the most important contributions made by CRI scientists in the area of adoptive cell therapy include:

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Adoptive Cell Therapy - Cancer Research Institute (CRI)