Scientists Identify Cancer 'Kill Switch'

Researchers in the US have discovered a cancer cell "kill switch", activated by a specific protein segment, that can pave the way for groundbreaking treatments. This discovery, which focuses on the exterior of tumor cells, is not only significant for the development of new cancer medications, but it also indicates the potential for strengthening present therapeutic procedures for fighting cancer.

For example, it has the potential to allow chimeric antigen receptor (CAR) T-cell therapy to be used against solid tumors such as those found in the breast, lung, and prostate. The new technique involves giving cancer patients T-cells that have been precisely designed to locate and eliminate tumors. 

 

The problem, according to Dr. Jogender Tushir-Singh, one of the researchers, is treating solid tumors since immune cells given intravenously struggle to permeate microenvironments and deliver therapeutic benefits. 

CD95 receptors, also known as Fas receptors, are found on the surface of cancer cells. When engaged, these receptors provide a signal that causes self-destruction. Despite the fact that these receptors have long been known about, attempts to activate them have been ineffective.

According to researchers at the UC Davis Comprehensive Cancer Center, a specific section on the receptor can activate the destruction process when targeted. The findings of their cell and mouse tests have been published in the journal Cell Death & Differentiation. 

 

Dr. Tushir-Singh said: 'Now that we've identified this epitope, there could be a therapeutic path forward to target Fas in tumors.'

 

Currently, conventional methods like surgery, chemotherapy, and radiotherapy remain the established protocols for treating cancer patients. However, children with leukemia and adults with lymphoma may have access to CAR T-cell therap

The process involves collecting and altering their own T cells, which are responsible for fighting off infections and other diseases but are unable to detect cancer cells. These customized cells are reintroduced into the bloodstream via intravenous infusion. Theoretically, these CAR T-cells are programmed to identify and combat cancer cells

Although effective against blood cancers, there is a chance of cancer recurrence in a small percentage of patients undergoing this treatment. Additionally, patients with solid tumors currently do not have access to this treatment. Dr. Tushir-Singh suggests that, theoretically, a treatment designed to target the cancer kill 'switch' could eradicate any remaining cancer cells post-CAR T-cell therapy. 

 

This has the potential to have a two-fold effect on cancers. Furthermore, it could support CAR T-cell treatment in solid tumors, although the mechanism is unknown. The research further indicates that individuals with a mutated epitope on their CD95 receptor fail to respond to CAR-T therapy. 

 

Dr. Tushir-Singh pointed out that changes in this epitope could be used to identify people who are candidates for CAR T-cell treatment. The team is presently developing a novel set of antibodies capable of attaching to and activating this specific kill switch. 

 

However, it is unknown whether this treatment will work and, if so, which malignancies it will be able to remove. Furthermore, the lengthy process of testing means that any new therapies require years before reaching patients.

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New Treatments for Multiple Myeloma

Multiple myeloma is a complex blood cancer characterized by the proliferation of malignant plasma cells within the bone marrow. Recent advancements in treatment have significantly improved patient outcomes, introducing innovative therapies that target the disease more precisely and effectively.

Traditional Treatment Approaches 

Historically, multiple myeloma has been managed through a combination of therapies: 

 

Chemotherapy: Utilizes cytotoxic drugs to kill rapidly dividing cancer cells. 

 

Corticosteroids: Help reduce inflammation and directly combat myeloma cells. 

 

Stem Cell Transplantation: Particularly autologous stem cell transplants (ASCT), where a patient's own stem cells are used to restore bone marrow function after high-dose chemotherapy. 

 

Radiation Therapy: Employed to control bone pain and treat localized disease.

Recent Advances in Treatment 

The past decade has witnessed remarkable progress in multiple myeloma treatment, with several novel therapies enhancing patient survival and quality of life: 

 

Proteasome Inhibitors: Drugs like bortezomib and carfilzomib disrupt cancer cell protein degradation, leading to cell death. 

 

Immunomodulatory Agents: Agents such as lenalidomide and pomalidomide modulate the immune system to target myeloma cells. 

 

Monoclonal Antibodies: Daratumumab and elotuzumab are designed to recognize and bind specific proteins on myeloma cells, marking them for destruction by the immune system. 

 

Recent promising developments: 

 

One notable advancement is the use of Blenrep (belantamab mafodotin), an antibody-drug conjugate targeting the B-cell maturation antigen (BCMA) on myeloma cells. Clinical trials have demonstrated that Blenrep, in combination with standard therapies like bortezomib and dexamethasone, can significantly reduce the risk of disease progression or death in patients with relapsed or refractory multiple myeloma. For instance, a recent study reported a 42% reduction in the risk of death when Blenrep was added to the treatment regimen. 

 

Another promising development is the approval of Elrexfio (elranatamab), a bispecific antibody that engages T-cells to target and destroy myeloma cells. Studies have shown that Elrexfio provides a median overall survival of more than two years in patients with relapsed or refractory multiple myeloma, highlighting its potential as an effective treatment option. 

 

Additionally, CAR T-cell therapies have emerged as a transformative approach in multiple myeloma treatment. These therapies involve modifying a patient's own T-cells to express chimeric antigen receptors (CARs) that specifically target myeloma cells. For example, Carvykti (ciltacabtagene autoleucel) has shown a 45% reduction in the risk of death in clinical studies, offering a one-time treatment alternative to ongoing drug regimens. 

 

These advancements underscore a dynamic shift in multiple myeloma treatment, with ongoing research poised to enhance patient outcomes and quality of life.

 

Prognosis and Conclusion 

The prognosis for multiple myeloma has improved significantly over the past decade, largely due to these therapeutic advancements. The overall five-year relative survival rate has increased to approximately 61.1%, with even better outcomes expected as new treatments continue to emerge. 

 

In conclusion, the landscape of multiple myeloma treatment is rapidly evolving, with recent developments offering renewed hope for patients. Ongoing research and clinical trials continue to explore innovative therapies and combination strategies, aiming to further improve survival rates and quality of life for those affected by this disease

 

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Types of Immunotherapy for Lymphoma

Your specialist may talk to you about using immunotherapy to help treat your lymphoma. It’s a new type of cancer treatment that works with your natural immune system to find and kill cancer cells in your body.
These are the different kinds of immunotherapy you may get for lymphoma:

• Monoclonal antibodies
• Immunomodulating drugs
• Immune checkpoint inhibitors
• CAR T-cell therapy

Monoclonal Antibodies

Your doctor will get your lymphoma cells tested to see if they have certain markers -- proteins called antigens. You’ll get a monoclonal antibody drug that aims at the antigens found on your lymphoma cells.
Monoclonal antibodies are made in a lab. They’re designed to lock onto certain antigens that cancer cells make too much of. This means that they affect mostly cancer cells with little damage to normal cells.
Monoclonal antibodies can work in -
 1. They keep cancer cells from growing by blocking signals sent out by the cancer cells. Blocking the signals stops these processes of the cancer cells growing.

2. They can also bind to the cancer cells and trigger your immune system to kill them. They may do this by marking the cells so your immune system attacks them. Or they can block the signals the cancer cells send out to tell your immune system to leave them alone.

3. Monoclonal antibodies can be attached to toxins, chemo, or radioactive substances. They then carry these cell-killing materials to the cancer cells and lock onto the antigen. This leads to the death of the cancer cells, with little to no effect on your normal cells that don’t have the antigen.

Here are some of the ways monoclonal antibodies can be used, depending on the type of lymphoma you have:
Follicular lymphoma: If you have a large stage I or II, or a certain kind of stage III or IV follicular lymphoma, your first treatment will likely be rituximab and chemo. You might get radiation, too. Then, if the lymphoma shrinks or goes away, you may get rituximab alone as maintenance therapy.
You can get rituximab alone or along with different chemo if the lymphoma comes back after treatment or stops responding to the treatment you’re getting.
Ibritumomab (Zevalin) or obinutuzumab (Gazyva) are other monoclonal antibodies you might get instead of rituximab.

Mantle call lymphomas: You might get rituximab along with chemo as the first treatment for mantle cell lymphoma. You can also get rituximab as maintenance treatment or if the lymphoma comes back.

Diffuse large B-cell lymphoma: You will get rituximab along with chemo for any stage of diffuse large B-cell lymphoma (DLBCL). You may also get radiation afterward.
You may get a monoclonal antibody called pembrolizumab (Keytruda) if the lymphoma comes back or doesn’t respond to the treatment with rituximab.

Burkitt lymphoma: Doctors can use rituximab to treat Burkitt lymphoma as your first treatment or as a later treatment. You’ll get it along with chemo.

Marginal zone lymphomas: Both gastric and non-gastric MALT lymphomas can be treated with rituximab. So can nodal and splenic marginal zone lymphomas. If you have any stage of one of these cancers, you might get rituximab, often along with chemo, as one of your treatments. You may also get it if the cancer comes back.

Rituximab, alone or with chemo, might be the first treatment you get for lymphoma in your skin (cutaneous B-cell lymphoma). Doctors can also combine it with the drug hyaluronidase (this is called Rituxan Hycela) and give it as a shot right into the skin lymphoma if it’s only in one area.

You might get a different monoclonal antibody, brentuximab vedotin (Adcetris), by IV if other treatments haven’t worked. Alemtuzumab (Campath) is another option if the lymphoma comes back after other treatments. You might get it by IV or as a shot into the skin lymphoma.

Hodgkin's lymphoma: You may get a monoclonal antibody called brentuximab vedotin (Adcetris) if you can’t have a stem cell transplant or classic Hodgkin's lymphoma comes back after treatment. You might get this as part of your first treatment if you have certain symptoms and blood test results. This drug binds to the CD30 antigen, which is common on Hodgkin's lymphoma cells. It’s attached to a chemo drug, which then kills the cell.

You can get rituximab along with chemo and radiation if you have early stage nodular lymphocyte predominant Hodgkin's disease (NLPHD) that’s causing symptoms or large tumors. You can also get it if you have more advanced-stage NLPHD, either alone or with chemo, and maybe radiation.

T-cell lymphomas: If your lymphoma stops responding to chemo, your doctor may talk to you about trying the monoclonal antibody called alemtuzumab (Campath) or brentuximab vedotin (Adcetris).

Immunomodulating Drugs

These drugs help your immune system work better, but doctors don’t know exactly how they work. The two drugs used are thalidomide (Thalomid) and lenalidomide (Revlimid).
You may get one of these drugs if you have one of these types of non-Hodgkin's lymphoma (NHL): a T-cell lymphoma; or a follicular, marginal zone, mantle cell, or diffuse large B-cell lymphoma. You might also get one of these drugs if you have Hodgkin's lymphoma that hasn’t responded to other treatments or that came back after treatment.
You can only get these drugs if you agree to take special precautions to prevent pregnancy because they cause severe birth defects.

Immune Checkpoint Inhibitors

Cells have proteins on them called checkpoints. They help your immune system know the difference between good and bad cells. Lymphoma cells can make these checkpoints and trick your immune system into not killing them. These drugs help keep this from happening.
For example, PD-1 is a checkpoint on your T cells. When it binds to the protein called PD-L1 on another cell, the T cell is stopped from killing that cell. Your Hodgkin's lymphoma cells may make a lot of PD-L1. This tells your T cells to leave them alone. There are drugs that can block PD-1. This means your T cells aren’t turned off and your immune system can attack the cancer cells.

Classic Hodgkin's lymphoma: If the lymphoma has continued to grow while you’re getting other treatment that includes a monoclonal antibody, nivolumab (Opdivo) may be an option.
If you have a stage III or IV Hodgkin's lymphoma that’s not responding to chemo or monoclonal antibodies, or has come back after a transplant, nivolumab or pembrolizumab (Keytruda) might be helpful.

CAR T-Cell Therapy

This is a very new treatment used for some types of B-cell lymphoma. CAR stands for chimeric antigen receptor. CARs are designed to lock onto antigens found on your lymphoma cells. Each patient has their own CAR T cells made just for them.

To do this, you get some T cells filtered out of your blood to make CARs in a lab. These cells are multiplies and injected back, so that the CAR T cells travel through your blood to find, lock onto, and kill the cancer cells. They continue to grow and multiply in your body so that CAR T cells can go on to kill cancer cells for months, or maybe even years.

Your doctor may talk to you about CAR T-cell therapy if you have diffuse large B-cell lymphoma (DLBCL) that’s not responding to other treatments. It’s also approved to treat relapsed or refractory primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

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