How Genetically Modified HIV Viruses Could Speed up Cancer Treatment

For the past 75 years, cancer has consistently been one of the top two causes of death in the United States, second only to heart disease. One in six deaths, globally, is attributed to cancer, and the disease has a 10-year mortality rate of around 50 percent. Cancer is very difficult to successfully treat, and scientists have been working to fight the disease for decades. However, recent developments have proven effective in combating certain cancers.

Cancers develop when the normal functioning and regulation of a cell gets disrupted. Cells can become cancerous for a variety of reasons—the most common being mutations either inherited or caused by environmental factors. When a cell mutates and becomes cancerous, it is able to grow and divide in the absence of growth signals; ignore the body’s signals for apoptosis (programmed cell death); and stop normal cells from growing. Cancerous cells continue to drain up the body’s resources and harm normal cells. Through a process called metastasis, cancerous cells spread from a singular tumor to other parts of the body, making cancer even more fatal.

Cancer cells are able to develop and metastasize because they can avoid detection by the immune system. While our immune system is designed to recognize and eliminate things that are potentially harmful, many tumor cells are not initially flagged by the immune system as harmful because they often appear as normal body cells. Tumor cells do this through various mechanisms, such as reducing the number of recognizable cancer proteins they produce. 

Luckily, scientists have developed a treatment that might address this hiding mechanism. First approved in 2017, Chimeric antigen receptor (synthetically designed antigen receptor) T-cell (CAR T) therapies modify the immune system to help it detect and destroy cancerous cells. This treatment genetically modifies T cells—which detect antigens on the surface of other cells that the body considers harmful—to recognize the proteins or antigens that cancerous cells produce yet normal cells do not. T cells detect foreign antigens using antigen-binding proteins on their surface. These proteins interlock with the antigens of harmful cells and signal to the immune system to destroy them. 

Typically, T cells used in CAR T therapy are modified outside of the body—a process known as ex-vivo CAR T therapy. First, the patient's blood is collected, and T cells are filtered out of this blood sample. Next, the T cells are genetically modified in a lab to express the CAR proteins, so they can detect cancer cells. The T cells are grown for several weeks so that they reach a sufficient number—usually a few hundred million. Finally, the T cells are sent back and infused into the patient’s blood.

This process is highly effective, especially in blood cancers; in one study, CAR T therapy eliminated cancer in around 80 percent of patients with advanced follicular lymphoma—a form of blood cancer—for which all other treatments had been unsuccessful. However, a major drawback of the current process is the amount of time and resources needed for this treatment. For a single patient, it takes around three to five weeks from the day of original blood collection for T cells to be ready for reintroduction into the patient’s body. This process of individual CAR T-cell generation is also very costly—often around half a million dollars for a single therapy. Because of the level of resources needed to carry it out, the therapy is only usually available to patients with very advanced stages of cancer. Furthermore, patients need to undergo a process known as lymphodepletion, in which high doses of chemotherapy are administered to get rid of existing immune cells so that the engineered T cells can take hold. Lymphodepletion not only causes complications related to cytopenia (low levels of blood cells) but can also make the patient more susceptible to various infections. This process is generally performed in a hospital setting to manage the potential risks, adding an extra layer of prohibitive costs.

Given the extraordinary success of CAR T therapies in treating patients with advanced cancer, researchers have been looking at ways for these therapies to be made accessible for a larger population while circumventing the lymphodepletion step. The main reason that ex-vivo CAR T is so time-consuming and expensive is because it requires removing, modifying, and then reinserting T cells. What if the T cells could just be modified inside the patient’s body?

Compared to ex-vivo CAR T, in-vivo versions of the therapy aim to modify T cells in the blood itself. The same mechanism used for ex-vivo CAR T therapy doesn’t work for in-vivo CAR T, since T cells are surrounded by other cells in the blood that doctors don’t want to receive the genetic modification. Researchers need a way to specifically target T cells for modification.

This is where HIV viruses come into play. HIV viruses are part of a family of viruses known as lentiviruses, which are a type of retrovirus. HIV viruses contain RNA code inside a protein shell, and when they infect a host cell, HIV viruses use the host’s DNA to replicate themselves. HIV viruses, in particular, target immune cells in the human body and are highly specific to T cells. HIV viruses normally use this ability to hijack the body’s immune system; however, by modifying these viruses’ genes, the immunosuppressive effects can be removed.

The natural specificity that HIV viruses have towards infecting T cells makes them the perfect delivery vehicle for in-vivo CAR T. HIV viruses can be modified to have their disease-causing genetic material replaced with the genetic code for the desired modifications to the antigen binding sites of the T cells. These modified HIV viruses can be directly inserted into the bloodstream, where they will directly modify a large number of T cells to have the desired cancer fighting property. 

Quite a few in-vivo CAR T therapies are currently under testing; many trials are set to start in 2025 or 2026. Although scientists still await the results of these clinical trials to determine the effectiveness of in-vivo CAR T therapies, in-vivo CAR T holds much potential for making cancer treatment—and possibly treatment for other conditions—much more accessible and efficient.