Development of an In Situ Cancer Vaccine via Combinational Radiation and Bacterial‐Membrane‐Coated Nanoparticles

Abstract

Neoantigens induced by random mutations and specific to an individual's cancer are the most important tumor antigens recognized by T cells. Among immunologically “cold” tumors, limited recognition of tumor neoantigens results in the absence of a de novo antitumor immune response. These “cold” tumors present a clinical challenge as they are poorly responsive to most immunotherapies, including immune checkpoint inhibitors (ICIs). Radiation therapy (RT) can enhance immune recognition of “cold” tumors, resulting in a more diversified antitumor T‐cell response, yet RT alone rarely results in a systemic antitumor immune response. Therefore, a multifunctional bacterial membrane‐coated nanoparticle (BNP) composed of an immune activating PC7A/CpG polyplex core coated with bacterial membrane and imide groups to enhance antigen retrieval is developed. This BNP can capture cancer neoantigens following RT, enhance their uptake in dendritic cells (DCs), and facilitate their cross presentation to stimulate an antitumor T‐cell response. In mice bearing syngeneic melanoma or neuroblastoma, treatment with BNP+RT results in activation of DCs and effector T cells, marked tumor regression, and tumor‐specific antitumor immune memory. This BNP facilitates in situ immune recognition of a radiated tumor, enabling a novel personalized approach to cancer immunotherapy using off‐the‐shelf therapeutics.

Engineering precision nanoparticles for drug delivery

“…The usage of photothermal NPs can improve the infiltration and activity of chimeric antigen receptor (CAR) T cells against solid tumours 69 . NPs can also be used to modulate immune activation or suppression to sensitize cancer cells to therapeutics, helping to homogenize these currently heterogeneous environments in an attempt to increase the number of patients who respond to or qualify for precision treatments 40 , 70 .…”

Bacteria‐Derived Nanoparticles: Multifunctional Containers for Diagnostic and Therapeutic Applications

“…[ 9 ] Membrane coating is composed of several steps, including modifying the bacteria and isolating and coating the membrane with a substrate. [ 72 ] There are various methods used to modify bacteria, such as imposition of stress conditions (e.g., temperature extremes, nutrient depletion, or antibiotic exposure), [ 22 ] which alter the type or density of surface‐associated or extracellular virulence factors. Membrane isolation can subsequently be achieved using multigelation, hypotonic damage, and ultrasonic disruption.…”

“…Synthetic nanoparticles coated with cellular membranes have been a common application. [71,72] While retaining complex bacterial characteristics and simulating their presentation as natural antigens to the immune system, the synthetic nanoparticle core provides adjustable physicochemical properties, such as particle size and shape, to optimally present antigens to immune cells. Therefore, nanoparticles encapsulated in bacterial membranes combine the advantages of both components.…”

Improving Cancer Immunotherapy Outcomes Using Biomaterials

“…[33] Bacterial cytoplasmic membranes may be employed to target tumors or used as adjuvants for enhanced immunotherapy. [34] Growing evidence suggests that the microbiome can influence diverse human diseases,i ncluding cancer. [35] Modulating the gut microbiome may impact outcomes of cancer immunotherapy,e specially for immune checkpoint blockade-based therapies.…”