Cancer Models Forum

Posted by Ruth, September 2019

4 promising therapeutic approaches being developed in the fight against cancer

With the growing interest in precision medicine amongst the translational oncology community, cancer therapeutics is seeing an increase in the development of personalised cancer treatments. As this happens, novel targets and methods are being investigated by major biopharmas, as well as biotechs fresh on the scene, with the hope of bringing novel treatments to cancer patients.

This summer we’ve been inspired by some of the innovative cancer therapeutics currently in development. So much so that we just had to write a blog post highlighting just four of the promising new treatment approaches being developed right now.

CRISPR/Cas9: The significance of molecular scissors in oncology

It is widely recognised that the manipulation of the prokaryotic CRISPR/Cas system (specifically using the Cas9 endonuclease) could hold the key in the fight against many genetic illnesses. The ability to essentially cut out faulty, disease-causing genes - and in some cases insert functional copies via natural DNA repair mechanisms - could offer a long-term cure for genetically defined diseases.

CRISPR Therapeutics applies CRISPR/Cas9 directly to cancer, using the technology to fuel next-generation cancer therapies, through precise and efficient editing of T cells and their expressed receptors. Here, CRISPR/Cas9 could radicalise existing CAR-T treatments by cutting down on the waiting time required to generate/harvest autologous T cells to be re-engineered for targeting tumour-specific antigens, and providing a useful tool in precision medicine to individualise the tumour-specific antigens that can be recognised. Why harvest these cells when we could create a bank of off-the-shelf genetically edited T cells ready for transfusion?

CRISPR/Cas9 also has in vivo potential, offering the ability to edit T cells, for example, in the body, after controlled delivery of the components systematically or to the target organ. CRISPR Therapeutics hopes to harness this potential by using viral and non-viral methods of delivery for the CRISPR/Cas9 components. More ambitiously, the editing of known oncogenes or even mutations for genetically-defined cancers could be performed; the complex and polygenic nature of cancer as a disease, however, further complicates this angle.

Anti-Tag Chimeric Antigen Receptor (AT-CAR): A twist on traditional immuno-oncology

Living Pharma is going one step further in the fight to overcome immunosuppression induced by cancer cells with their Anti-Tag Chimeric Antigen Receptor (AT-CAR) cell therapy. Unlike traditional CAR-T in which T cells are genetically engineered ex vivo to recognise a single tumour-associated antigen, the AT-CAR T cell is cleverly designed to have affinity for a variety of tumour-associated antigens on a patient’s tumour; this is key to preventing relapse often seen with CAR-T treatment.

The technology works by making use of antibody-tag conjugates (ATCs) ™ as mediators between the universal AT-CAR T cells and the cancer cells. The ATCs used can be varied to cover a wide range of tumour antigens helping to avoid resistance developing, with the same AT-CAR T cells for recognition and subsequent destruction of the cancer cells via the immune response generated with each round of treatment. If relapse does occur, Living Pharma is looking at whether the dose of ATCs could be adjusted, with the persisting AT-CARs remaining in the patient to recognise the newly tagged antibodies.

Natural Killer cells: The immune system’s secret cancer-killing weapon

Natural Killer (NK) cells are a key component of the innate immune response, acting as the first line of defence upon infection, with a unique ability to recruit the adaptive arm of the immune system.

For nkarta Therapeutics this naturally makes them a therapeutic target in the field of immuno-oncology. By culturing and genetically engineering NK cells to have enhanced recognition of tumour targets, nkarta Therapeutics’ approach involves directing an abundant amount of NK cells to tumours in order to encourage cancer cell destruction. And choosing NK cells over T cells comes with some advantages, such as greater control to prevent the occurrence of cytokine storms, as well as increased cytotoxicity.

Bacterial inside-out destruction: The promise of ninja bacs

Following observations made by William B. Coley in the 1890s of cancer allegedly being cured in post-operative patients who developed bacterial infections, it was established that the hypoxic environment within tumours provided hospitable conditions for anaerobic bacteria. Within this ideal environment the bacteria cells appear to act as tumour fighters, essentially killing the cancer cells as the infective process ensues and the bacterial cells rapidly divide. This effect also has the potential to be contained within the tumour environment by using commonly available antibiotics, preventing a systemic infection and destruction of non-cancer cells. Additionally, tumour-fighting bacteria have been found to initiate the patient’s immune response to help in the fight against the cancerous cells.

With Clostridium novyi-NT (CNV-NT), a Clostridium novyi strain without its lethal toxin, BioMed Valley Discoveries is working to fine-tune the system, minimising the adverse effects associated with bacteria and the toxins they produce. The company is currently completing a clinical research study of CNV-NT in combination with FDA-approved pembrolizumab, in patients with advanced solid tumours, to determine the highest tolerable dose.

The high mutation rate associated with cancer cells means that it is important to constantly improve on current therapies, as well as develop new approaches to curb growth and destroy cancerous cells. Additionally, as our knowledge on the impact of interpersonal variation on disease outcome and treatment response in oncology deepens, an increasing number of precision medicines must be developed to meet individual needs. These four approaches, to name a few of the many innovative precision cancer medicines in development, offer the possibility of doing just that. As these therapies are mostly in the early stages of development, however, having access to the right preclinical cancer models will prove crucial in their advancement to the clinic.

Want to know more about how the cancer drug development process needs to change to bring personalised treatments to patients? We recently held a webinar with a panel of industry experts about this key topic - read our blog post to see our key takeaways!

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