We have been in the laboratories where new molecules are studied and we discovered how biology and chemistry come together to develop increasingly targeted and precise treatments against tumors.
“The cancer diagnosis is really only part of the story.” I often hear this phrase repeated while I am at the pharmacological research campus in Beerse, an hour from Brussels. In fact, a few weeks ago I entered the laboratories of Johnson & Johnson’s only end-to-end hub in Europe, where around 4 thousand people, including researchers and technicians, work on all the main phases of the development path of a drug: from initial research to production.
And it is precisely by talking to them that we understand how we are already living in a new era of cancer treatment. CAR-T, or the genetic modification of lymphocytes to make them more effective in eliminating tumor cells, represents a well-established example of “how advances in the knowledge of cancer biology and the tumor microenvironment can translate into completely new therapeutic approaches”, says Ulrike Philippar, Vice President of the Oncology division and global head of research for new drugs for blood cancers and solid tumors at Johnson & Johnson.
An increasingly personalized approach
And from here we start to go further. In front of me, behind glass that insulates the environment and keeps the temperature between -20°C and -80°C, I see high shelves full of test tubes. They store around 2 million molecules, potential active ingredients ready to be studied and tested. The large scientific library on campus.
Many of these molecules are candidates to become new anti-tumor therapeutic approaches and all are linked by a common denominator: the increasingly personalized approach calibrated to the genetic characteristics of the individual tumor and the individual patient. “Rather than relying on a single technology, the goal is to match the most appropriate therapeutic modality to a specific target, tumor biology or disease mechanism,” confirms Philippar.
New therapeutic platforms
For example, there are multispecific antibodies, that is, antibodies designed to recognize and bind simultaneously to two different molecular targets, thus acting as a bridge between the tumor cell and the T lymphocyte that must fight it. Some bispecific antibodies are already used in clinical practice, as are some radio-enhancer drugs, which enhance radiotherapy. For the latter, we are now working on an evolution that involves the use of nanoparticles to be introduced directly into the tumor, to locally increase the effects of radiation and the damage inflicted on tumor cells.
However, platforms such as RIPTAC are still in a completely experimental phase (Regulated Induced Proximity Targeting Chimera), that is, molecules designed to simultaneously bind to two proteins, one typical of tumor cells and the other essential for their survival, to promote their death.
As well as in vivo CAR-T, i.e. the possibility of modifying T lymphocytes directly in the patient’s body to reduce times and increase their effectiveness.
And perhaps, even fewer side effects
The aim, we understand, is to “exploit the unique characteristics of tumor cells that distinguish them from healthy cells”, in order to refine the weapons with which we fight the disease and at the same time reduce its possible side effects. «Administering therapies in a more selective way will allow us to improve the results but also the tolerability profile and therefore the aspects linked to the patient’s quality of life», confirms Philippar.
A heart made up of many disciplines
And therefore the task of biologists is to understand how tumors grow, escape the immune system and interact with the microenvironment that surrounds them, in order to identify the most promising targets and select the most appropriate therapeutic approach. But once imagined, the new molecule must also be designed and built. And this is where chemists come in, working on the same campus, shoulder to shoulder with biologists.
It is no coincidence that, as they lead me into the heart of the research hub, I do not find myself in a laboratory full of test tubes but in an open space with tables and armchairs, where experts in different fields can sit and discuss. «Scientific inspiration usually comes from a question, rather than an answer. In many cases, innovation arises from the union of skills and today biologists, engineers, data scientists, chemists and so on sit together to tackle increasingly complex challenges.”
Not just artificial intelligence
What accelerates the research and development process, adds Philippar, are the new technologies that allow us to process increasingly large amounts of data, reducing efforts and optimizing times. Not only artificial intelligence, but also new generation sequencing which allows the rapid identification of genetic mutations in cells that may have contributed to the development of the tumor, or multiomics, which combines different levels of analysis and allows, for example, to understand what the consequences of these genetic alterations are. And again, once the molecule has been designed, computational models allow an immediate simulation of how it could interact with the target protein: the most promising candidates are thus identified and then subjected to laboratory experiments.
These technologies “are applied throughout the entire development process, including in clinical trial planning, patient recruitment and manufacturing, helping researchers generate scientific evidence more efficiently,” Philippar clarifies.
An encouraging historical period
Never before have researchers had so many tools to address the complex biology of cancer as in this historical period. And the results can be seen in the expansion of therapeutic possibilities that complement standard treatments. In short, although cancer diagnoses are growing (57% more diagnoses are expected by 2050), we have more and more options to deal with each individual case.
