Latest developments in cellular and gene therapies


Although numerous cellular and gene therapy products are currently in different phases of clinical trials, only 14 have been approved for use by FDA to date

Latest developments in cellular and gene therapies

Global market outlooks predict that the autologous cell therapy market will jump from $3.8 billion in 2015 to $23.7 billion in 2024. The stem cell therapy market, which utilises both autologous and allogeneic cell therapies, is expected to reach $170.1 billion by 2020.

The next few years will undoubtedly shift the pharmaceutical paradigm as therapeutics move from mass-produced to patient-specific.

How cellular and gene therapies work

Roughly speaking, cellular and gene therapy products differ from conventional therapeutics in that they harness the body’s natural bioprocesses instead of relying on foreign compounds.

At the highest level of differentiation, cellular therapy is either autologous or allogeneic. Autologous cell therapy uses the patient’s own cells, whereas allogeneic therapies use donor cells.

The least complex form of autologous cell therapy is regenerative, in that cells are extracted from the patient, proliferated and then reintroduced to the same patient. An example of this type of the treatment occurs in burn wards, in which a biopsy of a burn victim’s skin cells is sent to a third party that grows the cells into a skin graft.

In a more dynamic approach to cellular therapy, the extracted cells are modified by some means during or before proliferation, and then those modified cells are reintroduced into either the patient’s body (autologous) or another patient’s body (allogeneic). The modification of extracted cells can occur in many different ways, such as culturing the cells in the presence of specific antigens, or by the use of gene therapy to produce specialised cells that are then reintroduced and proliferated within the patient's own body.

How stem cells enter into the equation

A way around the isolation of specific cell types is through the use of stem cells, which can be stimulated to differentiate into the specific cell type of interest. Stem cell differentiation can also be used therapeutically to proliferate a rare or malfunctioning cell type (that occurs naturally in the body but, because of an ailment or disease, is not functioning in a standard fashion). Therefore, stem cell acquisition and differentiation can occur in tandem with the above approaches of immunotherapy and gene therapy, or can be the means to an end for simple cell proliferation.

The cellular and gene therapy market

The autologous cell therapy market is expected to jump from $3.8 billion in 2015 to $23.7 billion in 2024, with an estimated compound annual growth rate (CAGR) of 21.9%. This market is dominated by hospitals, research facilities and ambulatory centres.1 The stem cell therapy market, which encompasses part of the autologous cell therapy market, is expected to be valued at $170.1 billion by 2020. Adult stem cells make up the largest portion of this market because of their low-risk of contamination during subculture and proliferation, and because they require little labour production and are highly compatible with the human body. During this same period, pluripotent stem cells (stem cells that are capable of differentiating into all of the cell types that make up the body) are expected to make a huge rise, with revenues estimated at $4.5 billion by 2020.2

The technologies that drive these varied forms of cell therapy, such as cell acquisition, cryopreservation, cell production, expansion and subculture make up a significant portion of the autologous and allogeneic market. For the stem cell market in particular, stem cell acquisition is the fundamental step and is therefore expected to dominate that market with revenues estimated at $10.9 billion by 2020.2

Although there are only 14 FDA-approved “cellular and gene therapy products,” there are more than 750 companies worldwide that declare themselves to be in the “regenerative medicine” market space (this label includes both cell and gene therapy companies). Of those companies, 391 are incorporated within the United States. When compared with 2015, 2016 saw a 21% increases in the number of cellular and gene therapy drugs in clinical trials, with 271 in Phase I, 465 in Phase II, and 66 cellular or gene therapy products in Phase III.3

Approved cellular and gene therapy products

The 14 FDA-approved products “include cellular immunotherapies and other types of both autologous and allogeneic cells for certain therapeutic indications, including adult and embryonic stem cells.”4 With this in mind, it’s important to note that FDA has not approved any stem cell-based products, except ones that utilise cord blood-derived haematopoietic progenitor cells.5

Some currently available therapies include Vericel’s Carticel, which is used to repair articular cartilage injuries in the knee. Carticel therapy involves the isolation of chondrocytes (cells that are known to maintain a healthy cartilage matrix) from cartilage harvested from the patient. The cells undergo a first round of culturing and then are cryofrozen, which allows for flexibility when scheduling surgery. Later, before surgery, these cells are further proliferated so that they can be reinserted into the patient’s damaged knee.

Further simple extraction, proliferation and reintroduction therapies include Epicel (the skin graft example previously mentioned) and LaViv, a therapy in which fibroblasts are isolated from a biopsy and then proliferated and locally reintroduced to improve the appearance of moderate to severe (nasolabial fold) wrinkles in adults.

Dendreon’s Provenge is an FDA-approved immunotherapy — more accurately labelled as an immunostimulant — for prostate cancer treatment. Provenge works by training a patient’s own T-cells — the cells responsible for identifying and eradicating foreign objects — to recognise a specific protein (an antigen) present on the surface of 95% of prostate cancer cells. Under normal cellular processes, this antigen goes undetected and therefore prostate cancer cells can proliferate. The Provenge therapy trains a patient’s antigen-presenting cells — the cells responsible for differentiating T-cells — by culturing them in the presence of this recombinant protein. When reintroduced into the patient’s body, these cells start differentiating T-cells that can readily identify and kill prostate cancer cells.

What’s in the pipeline?

As previously mentioned, there are more than 800 cellular and gene therapy products in clinical trials around the world. At this time, none of the FDA-approved therapies utilise genetically modified cells, and only one uses stem cells. But this will likely change in the coming years as many of the products currently in the pipeline use these two fundamental techniques.

Kite Pharma’s KTE-C19 therapy for chemorefractory aggressive non-Hodgkin lymphoma follows a similar paradigm to Provenge, but uses gene therapy instead of immunotherapy. Instead of “training” antigen-presenting cells, Kite Pharma’s approach is to collect T-cells and use gene-editing technology to engineer T-cells that are capable of recognising and killing cancer cells that would otherwise go undetected. Novartis’s CTL019 treatment features a similar mechanism (but different approach) to Kite Pharma and is further along in the pipeline.

There are also a number of interesting therapies that utilise stem cells that are currently in clinical trials. Brainstorm Cell Therapeutics’ NurOwn treatment for Lou Gehrig’s disease uses autologous mesenchymal stems cells, a multipotent stem cell that is processed to secrete a variety of neurotrophic factors (NTFs) that protect neurons against toxins. (Multipotent stem cells differ from pluripotent stem cells because they can only differentiate into a limited number of cell types.) This treatment has been shown to be effective in animal models of ALS, sciatic nerve injury, Parkinson’s disease, multiple sclerosis, optic nerve ischemia and Huntington’s disease. The novelty of this approach is that it essentially creates therapeutic factories within the body. Trigenix’s Cx601 for Crohn’s disease and perianal fistulas is another novel treatment to use stem cells because it is one of the few drugs in clinical trials that utilises allogeneic stem cells (donor stem cells).


In the next few years, many new cellular and gene therapy products will come to market, shifting the paradigm of mass-produced therapeutics to a more individualised approach. How pharmaceutical and contract manufacturing firms will cope with this shift from the automated, factory production, in which one batch of therapeutics treats thousands of patients, to a more individual autologous approach in which one batch treats only one patient, remains to be seen.

The success of an autologous cellular and gene therapy treatment may not rely solely on the procedure making its way through clinical trials but may depend on the company’s foresight in the scalability of treatment.6 Nonetheless, the market outlook paired with the ingenuity of products currently in the pipeline portrays a positive change in the pharmaceutical industry that will ultimately be beneficial to both pharmaceuticals and patients alike.