Targeted Antigen Loaded Liposomes (TALL)

The human immune system acts as a precision military force, seeking out and eliminating foreign invaders such as viruses, bacteria and cancer cells. In the case of cancer, immunotherapies that stimulate and reinforce this natural defense system are quickly emerging as first-line treatment for multiple tumor types. While they’ve contributed significantly to some patients’ survival, these therapies have limitations. In addition to high cost and potentially serious side effects, they work only for a specific and still fairly limited group of patients.

SRI Biosciences developed TALL as a means to trick the immune system into recognizing tumor cells as pathogen-infected cells. Essentially, TALL makes cancer cells look like they have the measles, exploiting the biological phenomenon known as recall immunity to encourage the human immune system to seek out and kill an invader it already knows how to fight.

SRI created TALL using the company’s novel FOX Three platform, which was developed to solve another critical drug development challenge: biotherapeutic compounds that have traditionally been difficult to deliver to the inside of cells and therefore make the targets inside those cells undruggable. FOX Three employs proprietary processes to identify unique peptide delivery agents (known as Molecular Guidance Systems, or MGS) that home to targeted cell types and deliver a therapeutic payload in a cell-specific fashion.

How it works

SRI scientists pack a synthetic peptide derived from the measles virus into neutral, stealth particles known as liposomes. They then attach tumor-targeting FOX Three MGSs to the surfaces of the liposomes. The MGSs home to tumor cells and, once there, the liposomes are transported into the tumor cells. The measles-derived peptide is then released inside the diseased cells and eventually presented on their surfaces, flagging them for the immune system. The measles ‘infected’ tumor cells are then targeted and killed by memory T cells, and the patient’s immune system clears the tumor.

The vast majority of humans worldwide have been vaccinated for measles, so the immune system already recognizes TALL and is primed to respond to it; once TALL peptides attach their biological red flags, immune cells flood into the tumor environment and begin killing those cells. Because TALL is tumor-cell specific, it leaves healthy cells untouched, reducing the potential for serious side effects.

Validation

Pre-clinical research evaluating TALL demonstrates that liposomes accumulated in targeted cancer cells and these cells were subsequently flagged with measles peptide. This generated a rapid and robust immune system response against the targeted tumor cells and a significant reduction in tumor growth.

Early research also suggests that the TALL system could greatly expand the benefits of existing cancer immunotherapies, including checkpoint inhibitors (CKIs). These drugs are rapidly becoming standard of care for many cancer types because – in those cancers that are readily recognized by the immune system and generate a significant immune response – they are very effective. Unfortunately, about 80 percent of cancers don’t naturally generate a significant immune system reaction. CKIs are far less effective in these patients.

“By helping the immune system more readily recognize these cancers, TALL can overcome this drawback. For example, in pre-clinical studies looking at breast and pancreatic cancers, combining TALL with a leading CKI led to a 90 percent reduction in tumor volumes as compared to using CKI alone.”

Partner with us

SRI Biosciences partners with commercial companies through research collaborations that lead to option and licensing agreements for further commercialization. We are actively seeking partners for the TALL program. For additional information and/or to explore partnership opportunities, please contact SRI Biosciences at biosciences@sri.com.

DECEMBER 2020