What is immunity?

The immune system includes a set of body defense against foreign bodies: infectious agents, but also transformations of a self-constituent, during the carcinogenesis process.

It is a complex system that can be by dividing it into two collaborative parts:

Innate immunity

  • Present in all live beings, it is able to attack any external or “abnormal” agent. It represents the first barrier of the immune system because it reacts nearly immediately against a pathological threat and transmits information, which mobilizes the other compartment of the system.
  • Innate Pharma has occupied a unique position in this field since the creation of the Company.

Adaptive immunity

  • Needs a few days to develop and is only present in vertebrates.
  • It is more specifically directed against pathogens and it generates "memory".
  • Adaptive immunity is activated, for instance, by the vaccination process but also by the new generation of immunomudalating antibodies like ipilimumab (anti-CTLA4, Bristol Myers-Squibb) or the anti-PD1/PDL1 in clinical trials.

The immune system consists of 2 parts:

 

From nonspecific immunotherapy to targeted immunotherapy

Immunotherapy, the concept that aims to ensure that the patient's immune system fights its own disease, is an "old" therapeutic approach, which dates back to 1890!

That year, for the first time, a young New York surgeon used bacterial toxins to treat patients with sarcomas. It was not until 1922, however, that the intuition of William Coley was confirmed by the demonstration that BCG (the vaccine against TB) is capable of stimulating the immune response. Oncologists today use this same BCG to treat localized bladder tumors.

Certain cytokines (the "messengers" of the immune system) such as interleukin 2 and interferon α in metastatic renal cell carcinoma or malignant melanoma at high risk have become standard treatment in oncology, but this occurs at the cost of serious side effects. Given the modest responses observed, the approach generated great skepticism among clinicians.

But over the past two decades, immunologists have made significant progress thanks to advances in imaging and molecular genetics.

Immunologists have established the main principles of the organization of the immune system, deciphered the biology of its cells, dissected the molecular cascades responsible for their activation, identified many tumor antigens and explored how cancer cells manage to escape the action of our immune system, they are now trying to predict its operation and manipulate it "at will".

These discoveries have already translated into clinical applications and gradually "dopants" (nonspecific immunity such as cytokines) are giving way to targeted immunotherapies.

As opposed to initiating a generalized activation of the immune system, these new immunotherapies are now capable of triggering the removal of tumor cells by killer cells (cytotoxic antibodies), which "teach" the patient's immune cells to recognize and destroy cancer cells (therapeutic vaccines), and to modulate selectively the activity of this or that group of white cells (immunomodulating antibodies).

 

Immuno-oncology: 30 years of innovation

The scientific revolution of targets

  • The first therapeutic targets were identified at the surface of tumor cells leading to antibodies recognizing them as “signals of malignant transformation”, binding to them and force their recognition and killing by effector cells, with NK cells being the most important of these.
  • New targets for immunotherapies are now found at the surface of effector cells: the strategy is to selectively activate a type of immune cells. These drugs are called immuno-modulating antibodies; the first one was approved in 2011. Most of the drugs in this area target adaptive immunity cells.
  • By deciphering the mechanisms of how cells of innate immunity function, new targets have been uncovered. These targets are on the surface of killer cells in innate immunity such as NK cells. The mechanism of action of antibodies derived from these targets is identical to that of immunomodulators of T cells: by blocking their inhibitory receptors, they activate NK cells and trigger tumor lysis.

 

Activation of the immune system


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