Product Spotlight: 3D(6-acyl)-PHAD®

Posted on December 21, 2021

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Why we need to accelerate renal cell carcinoma (RCC) research, and how we do it.

The bottom line is that RCC is one of the ten most globally common cancers and has been on the rise in the past decade. Since 2008, the number of new cancer cases has been increasing by roughly 1% per year. In 2021, an estimated 76,000 people were diagnosed with kidney cancer in the United States. It is the sixth most common cancer among men, and the ninth most common among women. This cancer has been a prime target of immunotherapies since the early 90s with the FDA’s approval of high-dose interleukin 2 and more recently with programmed cell death protein 1 antibody immune checkpoint blockade.

In preclinical research, the mouse renal adenocarcinoma model is used for evaluating new immunotherapies. CD8+ T-cell responses form the backbone of cancer immunotherapy. The formation of the peptide-major histocompatibility class I (MHC-I) T-cell receptor (TCR) complex initiates and executes the CD8+ T-cell response. These peptides are displayed on MHC-I surfaces of antigen-presenting cells (APCs) or target cells. At this point they are engaged by a CD8+ T-cell expressing an appropriate TCR for that neoepitope. The neoepitopes include tumor-specific MHC-I binding epitopes that are a huge source of personalized vaccine targets. Patients rarely share the same epitopes; so, identifying functional immunogenic targets is a challenge. Research has shown that dendritic cell vaccines with a “cocktail” of short peptide neoepitopes can be used to induce neoepitope-specific CD8+ T-cell responses in humans. A couple of months ago, we highlighted Dr. Jon Lovell’s research which created a CPQ (CoPoP/3D6APHAD/QS-21) liposome adjuvant system which potently induced Ag-specific CD8+ T-cell responses.

Well, our friend, and November’s Lipid Leader, Dr. Jon Lovell is at it again! He recently published another paper using Avanti’s 3D(6-acyl)-PHAD® product! The MPLA structural analog, 3D(6-acyl)-PHAD®, is the synthetic MPLA most closely related to the reported structure of MPL® Adjuvant used in GSK’s Adjuvant Systems AS01, AS02, and AS04. As with other synthetic MPLA analogs manufactured by Avanti, it is structurally homogeneous and highly purified, and mimics the TLR4 agonist activity of bacterial MPLA. Alright, enough about what the product is, let’s look at how Dr. Lovell used this adjuvant in his research at the State University of New York at Buffalo! We highly recommend reading the full article by clicking HERE but keep reading to see the conclusions that were drawn from this research!

Was the CPQ liposome adjuvant system capable of the desired CD8+ T-cell response?

In short, YES! In fact, this system was found to be critical of inducing a neoepitope-specific CD8+ T-cell response. For comparison, they also used a traditional adjuvant system, poly (I:C), and found that it was insufficient to induce the same response even at a 1000-times peptide dose. The neoepitope immune response was potent and provided immunization against orthotopic, metastatic, and primary tumors. These results prove that multivalent particle immunization and neoepitope discovery of cancer immunotherapies! Job well done, Dr. Lovell!

The CPQ liposome adjuvant vaccines were prepared using DOPC, plant cholesterol, 3D6APHAD, and QS-21, all of which can be found on the Avanti or Croda websites. Click each product to learn more and make a purchase!