2021-001 COMBINATION CHEMO-IMMUNOTHERAPY FOR PANCREATIC CANCER USING THE IMMUNOGENIC EFFECTS OF AN IRINOTECAN SILICASOME NANOCARRIER PLUS ANTI-PD-1

SUMMARY

UCLA researchers in the Department of Medicine have developed a combination therapy for pancreatic cancers using the irinotecan Silicasome nanocarrier and an anti-PD-1 antibody.

BACKGROUND:

Immune checkpoint inhibitors (ICIs) has shown promising therapeutic effects for the treatment of cancers such as renal and lung cancer. However, there has been little success in the use of immune checkpoint blocking antibodies in pancreatic ductal adenocarcinoma (PDAC). While anti-PD-1 antibody (Keytruda^®) was approved for PDAC patients with rare genetic mutations (i.e. microsatellite instability or mismatch repair deficiency), this treatment option impacts less than 1% of cases. With the current standard of care options, the 5-year survival rate of PDAC is only ~8%. Novel and effective treatments are needed for PDAC patients.

INNOVATION

Dr. Andre Nel and colleagues in the Department of Medicine have developed a combination therapy for PDAC using the irinotecan silicasome nanocarrier and anti-PD-1 antibody. The key advance is the enhanced delivery of a traditional anti-PDAC chemo agent, irinotecan, via the novel silicasome nanocarrier.  The carrier is comprised of mesoporous silica nanoparticles with a high interior packaging space into which the irinotecan is remotely imported and trapped by a surface coated lipid bilayer.  The scientists demonstrated that irinotecan triggers robust anti-tumor immunity by initiating immunogenic cell death, which enhances the uptake of debt tumor cells by the immune system.  The response was accompanied by increased PD-L1 expression.  The generation of tumor cell death and the immune response is indicative of the increased irinotecan delivery at the cancer site, without evidence of toxicity. The induced PD-L1 expression triggered by irinotecan allows robust synergy between the immunogenic cell death response, and co-administration of anti-PD-1 antibody.  The combination of chemo-chemoimmunotherapy plus the synergy with anti-PD1 allowed the silicasomes nanocarrier to outperform the therapeutic effects of a commercially available irinotecan liposome, Onivyde.

POTENTIAL APPLICATIONS:

• Treatment for pancreatic cancers

 ADVANTAGES:

• Enhanced chemotherapy delivery by the silicasome
• Silicasome is devoid of systemic toxicity
• Irinotecan delivery also imparts an immunogenic response, a concept known as chemo-chemo-immunotherapy
• The immunotherapy response can be further enhanced by anti-PD1

DEVELOPMENT-TO-DATE:

The study has been validated in the mouse model.