The past: “Classical” cancer therapies
Classical cancer therapies include chemotherapy, radiotherapy, and surgery. Unfortunately, these remain the sole therapeutic option for many individuals who receive a cancer diagnosis. In the latest release of the Canadian Cancer Society’s annual report on cancer incidence, it’s estimated that 2 in 5 of Canadians will be diagnosed with cancer during their lifetime. With those odds, while you may be spared, someone you love might not. Luckily, cancer researchers in Canada are working hard to change this narrative.
When most think of cancer therapy, they envision toxic chemotherapies that target and eliminate the body’s fastest-growing cells. They kill anything that rapidly divides – cancer or not. Unfortunately, these treatments lead to many harsh side effects including; hair loss, suppressed immunity, nausea, neuropathy (nervous system damage/ dysfunction), and others. These side effects emerge when the rapidly dividing non-cancerous cells inevitably become exposed and killed. Perhaps these side effects would be tolerable to some, particularly if the trade-off is moving forward cancer-free. However, for many patients, this isn’t the case. While chemotherapy may initially work, shrinking tumours, they often eventually fail. These resurgent cancer cells tend to be more aggressive and less treatable.
The present: Adoptive Cell Transfers
Today many emerging therapies have demonstrated an alternate narrative. This includes an emerging “living drug” class called adoptive cell transfers (ACT). The fundamental science behind the current ACT is the same that underpins vaccines. Both strategies train the immune system to respond to infections (vaccines) or cancer (ACT). Vaccines are created with bits of the pathogen of interest; for example, COVID-19 vaccines use a portion of the spike protein to train the immune system. Unfortunately, because cancer cells are self, they’re not as easily identified by the immune system. Luckily, many tumours harbour unique genetic mutations. These can be targeted to help the immune distinguish between healthy and cancer cells.
The ACT regimen begins with isolating immune cells from an individual. Next, these cells are taken to the laboratory, where they are expanded (replicated/ grown) and “trained” to recognize cancer more effectively. Then millions of these more competent anti-cancer immune cells are infused into cancer patients. These immune cells retain their ability to distinguish cancer from self and recent studies have found that they persist in the body 10 years after initial infusion!
ACT can circumvent the toxic side effects of classical chemotherapy but can also lead to unique side effects. For example, side effects are commonly observed in patients who experience overstimulation of the immune system. This may lead to deadly inflammatory conditions, including cytokine release storm (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Unfortunately, we can’t accurately predict how someone will respond to ACT.
The future: The Transferred Cell
A healthy individual has several different kinds of immune cells, each with a specific job. For immunity to work effectively, the cells of the immune system need to function together. Despite this, most cancer researchers developing ACT transfer just one kind of immune cell at any point, mainly T cells. T cells come in several flavours, but their main job is carefully looking for their trained “signal.” In this case, it’s the target cancer-specific signal. However, other immune cells activated through different mechanisms may improve efficacy while decreasing side effects. For example, NK cells recognize “stressed” cells. They have already demonstrated an ability to reduce side effects in very early clinical trials. They are expected to be one of many improved efficacy ACT products designed in the years ahead.
The reality is that these therapies have only recently been integrated into clinical treatment regimens. Nevertheless, many ongoing ACT research projects and clinical trials suggest that these therapies will become more widely available to those who couldn’t be treated by the “classical” chemotherapies.