What Is Allogene Therapeutics?

Updated May 30, 2019

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When it comes to therapy, cancer patients have many options. They can receive one or more types of treatments, like surgery, chemotherapy, or radiation.

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It is important to know that your genes are not your destiny. There are various environmental and genetic factors working together to shape you. No matter your genetic makeup, maintain ideal blood pressure and glucose levels, avoid harmful alcohol intake, exercise regularly, get regular sleep. And for goodness sake, don't smoke.

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They can also get a combination of them. Still, despite this abundance of choices, many available treatments don’t work at all for some patients and those that do work tend to have side-effects that severely compromise patient health.

As a result, cancer researchers are always on a quest for the holy grail: a treatment that heals cancer but does not cause irreparable harm to the patient. They may have found it when they focused on an immunotherapeutic approach that genetically engineered T-cells to empower a patient’s own immune system to destroy cancer cells.

Now instead of using treatments that also harmed healthy cells, the body’s own defense system could specifically target cancer cells and destroy them.

Here at Your DNA, we will take a closer look at immune cell therapy, focusing on a new approach called allogenic CAR-T therapy pioneered by the clinical stage biotechnology company Allogene Therapeutics.

AlloCARs Therapy: A Revolution in Cancer Treatment

Before Allogene Therapeutics introduced AlloCARs Therapy, which is an allogenic CAR-T therapy 1, there was another cancer treatment called autologous CAR-T cell therapy 2 that appeared to be a major breakthrough in cancer treatment.

While autologous CAR-T therapies were the first revolution, AlloCARs therapy may be the next revolution.

Quick Overview

The First Revolution: Autologous CAR-T Therapies

The immune system defends the body against disease. Think of it as a defending army. Some of the soldiers in this army are more like commandos than infantry soldiers.

These are the T-Cells. Their mission is to target both infected and abnormal cells.

Unfortunately, impressive as T-cells might be, they are no match for cancer cells. Despite putting up a brave defense, they are outwitted, outmaneuvered, and outmatched by the ruthless march of cancer.

After reviewing how the immune system was overpowered by cancer cells, scientists created a super soldier — a tougher T-Cell that was smart enough to only seek out and destroy specific types of cancer cells.

Since superior T-cells are made, not born, scientists created a manufacturing process. Developing formidable, cancer-fighting T-cells requires the patient’s blood to be filtered through a machine that separates blood cells, separating T-cells and white blood cells from red blood cells.

Once T-cells have been harvested, they are equipped with an antenna to detect cancer cells in the bloodstream. This is engineered by mixing T-cells with a disabled virus.

Since the virus is now harmless, it can’t create illness; but what it can do is send genetic instructions to the T-cells to grow artificial receptors.

These newly-grown, artificial receptors are called CARs, which is short for “chimeric antigen receptor.” T-cells equipped with CARs are called CAR-T. The development of CAR-T made it possible for enhanced T-cells to track down and kill cancer cells.

The next challenge researchers faced was figuring out how to get enough CAR-T cells for a combat mission. They achieved this goal by growing millions of copies of reprogrammed T-cells in the laboratory.

The final stage was getting the millions of CAR-T cells to the battlefield. This was the easiest part of the whole process: patients were intravenously given back their own blood.

The results astonished medical scientists. Patients who had resisted other forms of cancer therapy now responded well.

Even the U.S. Food and Drug Administration (FDA) was impressed and approved the new therapy for two types of hematologic cancers — relapsed or refractory acute lymphoblastic leukemia and relapsed or refractory large B-cell lymphoma.

The Next Revolution: Allogenic CAR- T Therapy

Despite the success of adoptive cell therapies, there were some serious problems. These were not related to the therapy itself but were more in the nature of technical glitches — namely, issues related to manufacturing enhanced T-cells.

The first major problem was the high-cost involved in the process. It cost a lot of time and money to filter blood from a patient, isolate T-cells, reprogram them to detect cancer cells, cultivate millions of copies, and then reintroduce this immune-enhanced blood back into the patient.

The second problem was quality-control. Laboratory conditions had to be carefully controlled and medical technicians had to be highly-trained to always do an impeccable job.

Due to the complexity of the entire project, undetected mistakes could occur at any point in the painstakingly detailed process. If errors occurred, all the money spent on manufacturing robust T-cells would have been wasted and the patient might not be strong enough for retreatment.

AlloCARs therapy proposes to eliminate these two challenges. Instead of relying on a patient to provide the T-cells, medical technologists can get T-cells from a healthy donor that match the patient’s blood type.

Instead of relying on a manufacturing process for each patient, med techs can make enough reprogrammed T-cells for many patients with the same blood type. In addition, by manufacturing blood ahead of time, more time is available to use gene-editing technology to improve the quality of the blood.

What Is Allogene Therapeutics?

Allogene Therapeutics is a biotechnology company that has pioneered a potentially life-saving cancer treatment.

It’s on a mission to advance immune cell therapy for patients who have hematologic cancers and solid tumors. The general name for their treatment is allogeneic CAR-T but their proprietary process is called AlloCART™.

Management Team

The management team consists of world-class cell therapy experts The company was co-founded by Arie Belldegrun and David Chang. Belldegrun serves as the Allogene Therapeutics Executive Chairman while Chang serves as the Allogene Therapeutics CEO.

Company Overview

The goals of the company are to provide an “off-the-shelf" solution for CAR-T cell therapy. By using healthy donors to harvest immune cells and then genetically programming T- cells, they aspire to make cell therapy more easily available for more people at a lower cost.

By providing patients with already engineered cells for their type of cancer and blood type, production will be more efficient and cost-effective. Additionally, the turnaround time from the laboratory to the patients will be faster.

What Is the History of Allogene Therapeutics?

The revolution in immunotherapy for cancer treatments started when Novartis and Kite Pharma got FDA approval for autologous CAR-T therapies for the treatment of acute lymphoblastic leukemia (ALL) and other diseases.

These therapies were based on a simple but highly effective approach: use chimeric antigen receptor T- cells manufactured from the patients’ own T-cells.

Gilead Science purchased Kite Pharm for the price of $12 billion — despite the fact that the company only had one product which they had only recently entered into the marketplace.

That seemed the end of the story, but then something extraordinary happened. In 2018, two former Kite executives, Arie Belldegrun, founder of Kite, and David Chang, the former chief medical officer of Kite, formed Allogene Therapeutics and purchased the rights to CAR-T developmental programs.

They managed this buy-out because they were backed by $300 million Series A financing provided by a consortium of investment firms and venture capitalists. Since Pfizer owned some of the rights to the portfolio, it retained 25% ownership.

What Does Allogene Therapeutics Do?

Allogene Therapeutics is creating an alternative therapy to autologous CAR-T therapies.

They are using a gene-editing technology licensed from Cellectis to improve existing CAR-T therapies. Using TALENs (the gene editing technology) 3 they plan to minimize the risk of GvHD (graft vs host disease) 4 by editing out functional T-cell receptors (TCRs).They also plan to improve CAR-T cell proliferation within a patient’s body by removing CD52 and giving patients an anti-CD52 antibody.

What Products and Services Do Allogene Therapeutics Offer?

The company’s primary products, which they are calling AlloCARs, focus on further improving the standards of allogeneic CAR-T cell therapies.

Their pipeline of multiple allogeneic T-cell products aims to provide medical treatments for hematological malignancies, solid tumors, and lymphodepletion agent.

Why Is Allogeneic Cell Therapylymphodepletion Beneficial to Cancer Patients?

Allogenic cell therapy will eliminate many of the problems associated with autologous CAR-T therapy.

This includes reducing wait time for patients who have a poor prognosis as well as reducing unpredictable treatment results based on compromised T-cell potency.

Autologous CAR-T therapy also has inefficiencies of scale 5 which drive up the cost of logistics. Moreover, since there are no pre-existing inventories, retreatment of patients can be difficult.

What Process Does the Consumer Go Through?

Once the allogenic CAR-T therapy process has been fully developed, it is expected to make treatment for consumers easier by delivering product on demand from an existing inventory, by enhancing the potency of T-cells and white blood cells, and by improving the scale of efficiencies

— for instance, a single donor’s T-cells could be used to deliver matching engineered T-cells for up to a hundred patients.

Conclusion and Bigger Picture

Allogene Therapeutics cancer treatment plans are focusing on innovation rather than simply rebranding and commercializing autologous CAR-T therapy.

By developing allogenic CAR-T therapy, they will eliminate many autologous CAR-T therapy shortcomings.

Although Allogene Therapeutics did not invent allogenic immune therapy, they have a good chance of taking the techniques and technology to a whole new level. Allogene Therapeutics’ management team includes pioneers in cell therapy research and the company has plenty of financial backers to fund research.

In addition, they have more than enough clinical research portfolio assets to develop highly effective cancer-fighting products. Their portfolio includes 16-pre-clinical CAR-T cell therapy targets, as well as UCART19, a therapy in Phase 1 development for the treatment of relapsed or refractory acute lymphoblastic leukemia.

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Referenced Sources

  1. Allogeneic CAR-T Cells: More than Ease of Access?
    Charlotte Graham, Agnieszka Jozwik, Andrea Pepper, and Reuben Benjamin. Published online 01 Oct 2018.
  2. Chimeric Antigen Receptor T-Cells (CAR T-Cells) for Cancer Immunotherapy – Moving Target for Industry?
    Paula Salmikangas, corresponding author Niamh Kinsella, and Paul Chamberlain. Published online 31 May 2018.
  3. TALENs: a widely applicable technology for targeted genome editing.
    J. Keith Joung and Jeffry D. Sander. Published online 21 Nov 2012.
  4. Graft vs Host Disease: An Overview in Bone Marrow Transplant
  5. Industrializing Autologous Adoptive Immunotherapies: Manufacturing Advances and Challenges.
    Rohin K. Iyer, Paul A. Bowles, Howard Kim, and Aaron Dulgar-Tulloch. Published online 23 May 2018.