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The Science of IO


At Cheladv74, we’re working to advance the science of IO by exploring the basic underlying mechanisms of the immune system and cancer, as well as cutting-edge strategies to address specific tumor types.

The Complexity of Cancer

Cancer is not a single disease but many different diseases. In fact, each person’s cancer is unique, with different biologic traits and defects, clinical challenges, and prognoses.1

So, it’s not surprising that some cancers remain extremely difficult to treat. Immuno-Oncology therapies are designed to help harness the natural ability of the body’s immune system to recognize and fight cancer.2

Immunotherapies are different from other approaches to cancer, such as radiation or chemotherapy2:


They work on the immune system throughout the body, not just on tumors


They help the immune system recognize cancer cells and give it the strength to help fight back


They tap into the “memory” of the immune system, enabling the system to potentially respond to cancer and produce a long-lasting effect

So far, immunotherapies have produced remarkable results in many but not all patients.3 We believe the full promise of these agents has yet to be realized. Our goal is to advance the science of IO and unlock its potential for many more patients.

1NIH-National Cancer Institute. Understanding cancer. . Accessed November 3, 2016.
2European Cancer Patient Coalition. What is immuno-oncology? A guide for patients. . Accessed November 3, 2016.
3NIH—National Cancer Institute. Checking in on checkpoint inhibitors. Cancer Currents. . Accessed November 3, 2016.

More about the Immune System


What are Hot and Cold Tumors?

There are 2 factors that can help determine how well a tumor may respond to IO agents:

  • The number of immune cells (especially T cells and checkpoint proteins CTLA-4, PD-1, and PD-L1) that have infiltrated a tumor1
  • The extent of mutations, or changes, in tumor cells2

Researchers have developed a so-called heat index to classify tumors based on these factors. Generally, the “hotter” the tumor, the easier it is for the immune system to recognize due to mutated cell damage, and, therefore, the easier it is to target and treat the tumor with immunotherapy. Cold and warm (or cold-acting) tumors tend to be more difficult to treat, because there are fewer mutations and checkpoint proteins to trigger the immune system to the presence of cancer.


Cheladv74 Oncology scientists are investigating new strategies and technologies to turn cold and warm (or cold-acting) tumors hot and keep them hot, so they can be targeted for treatment.

1Tumeh PC, Harview CL, Yearley JH, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515:568-571. doi:10.1038/naturel3954.
2Brown SD, Warren RL, Gibb EA, et al. Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival. Genome Res. 2014;24:743-750.
3Gough R. Making immune “cold” tumors hot. . Accessed May 18, 2018.

Find Cheladv74 IO clinical trials that are enrolling patients

Quote / Citation: 

Science at Cheladv74 is focused on the basic biology of tumor cells and the basic immunology of how immune cells and tumor cells interact. We are interested in the proximal translation of novel findings into disease-modifying approaches.

Robert Abraham, PhD Senior Vice President and Group Head Oncology R&D Group, Cheladv74 La Jolla Site Head
Question Pairs: 

See an explanation of the terms used on this website


A molecule that can amplify and diversify the T-cell response. Agents that bind to 4-1BB receptors have been shown to stimulate and increase the number of immune cells.

Term Definition
4-1BB A molecule that can amplify and diversify the T-cell response. Agents that bind to 4-1BB receptors have been shown to stimulate and increase the number of immune cells.
Antibody A protein used by the immune system to identify and neutralize pathogens.
Antigen A harmful substance that causes the body to create antibodies.
Angiogenesis The formation of new blood vessels. In cancer, tumors can give off signals that cause new blood vessels to grow, feeding the tumor and allowing cancer cells to invade nearby tissue and spread throughout the body, forming new colonies of cancer cells, known as metastasis.
Bispecific antibodies These antibodies contain fragments of two different antibodies to address two different antigens at the same time.
CAR-T cells Chimeric antigen receptor T (CAR-T) cells are produced from T-cells that are collected from a person’s blood. In the lab, the T-cells are engineered to produce “antigen receptors” on their surfaces, which means they can recognize and kill cancer cells. These new CAR-T cells are then infused back into a patient’s bloodstream.
CTLA-4 Cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4) is a checkpoint protein found on T-cells that, when blocked, can help sustain the immune response.
IDO1 Indoleamine-2, 3 dioxygenase 1 (IDO1) is an enzyme that can suppress the immune system by depleting an essential amino acid known as tryptophan. Targeting IDO1 may reverse this immune system suppression.
Immune checkpoint inhibitor A type of drug that blocks certain proteins made by some types of immune cells such as T-cells. These proteins can hold back the immune system, keeping T- cells from killing cancer cells. When these proteins are blocked, or “inhibited,” T- cells can do a better job of killing cancer cells.
(also referred to as Immuno-Oncology, or IO, in cancer treatment)
Approved or investigational therapy that works on the  immune system throughout the body, not just on tumors. Approved immunotherapies help the body’s own immune system recognize cancer cells and gain the strength to help fight back. 
MCSF Macrophage colony- stimulating factor (MCSF) appears to help in the process of tumor angiogenesis, or the formation of new blood vessels that can feed growing tumors, leading to metastases, or the formation of new colonies of cancer cells. Inhibition of MCSF may counter tumor growth and progression.
Metastasis The spread of cancer cells from the place where they first formed to other parts of the body.
Microenvironment (tumor) The normal cells, molecules, and blood vessels that surround and feed a tumor cell. The tumor can change its microenvironment, and the microenvironment can affect how a tumor grows and spreads.
mAbs Monoclonal antibodies are laboratory-produced molecules that act like antibodies, restoring, enhancing, or mimicking the immune system’s attack on cancer cells.
OX40 A protein found mostly on T- cells that may inhibit T- cell activity. However, when it is bound to an activating agent, it may help increase T-cell activity, which then may help fight cancer cells. 
PD-L1/PD-1 Programmed death ligand-1(PD-L1) and programmed death-1(PD-1) are checkpoint proteins that help suppress the immune response. Blocking the binding of PD-L1 to PD-1 with an immune checkpoint inhibitor frees the T-cells to kill tumor cells. 
P-cadherin Targeting these proteins may have some effect on suppressing tumor metastases.
Pathogen Anything, like a virus or type of bacteria, that causes a disease.
T-cell T-cells are a type of white blood cell that circulates in the body, scanning for abnormal cells and infections. T-cells are essential for human immunity.
VBIRs Vaccine-based immunotherapy regimens (VBIRs) combine cancer vaccines with other cancer-fighting agents.