Interleukin-15 and cisplatin co-encapsulated thermosensitive polypeptide hydrogels for combined immuno-chemotherapy

Injectable Hydrogels as Unique Platforms for Local Chemotherapeutics‐Based Combination Antitumor Therapy

“…However, the undesirable toxicity of many chemotherapeutic drugs to T cells, natural killer (NK) cells, and dendritic cells (DCs) limits their combination with immunotherapeutics . To address the above challenges, several injectable hydrogel‐based depot systems have been designed to co‐deliver chemotherapeutics and immunotherapeutics for localized combination cancer therapy . The combination delivery systems are expected to not only maintain effective drug concentrations by prolonging the drug residence time at the tumor site, but also protect bioactive molecules against denaturation or degradation .…”

“…In a subsequent study, when a DOX/IL‐2/IFN‐γ co‐loaded hydrogels based on a poly(g‐ethyl‐ l ‐glutamate)‐poly(ethylene glycol)‐poly(g‐ethyl‐ l ‐glutamate) copolymer (PELG‐PEG‐PELG) triblock thermo‐sensitive copolymer was used to locally treat BALB/c mice bearing mouse (B16F10) melanoma xenografts, CD4 + and CD8 + T‐lymphocytes showed significantly increased proliferation that was suggested to be related to enhanced tumor cell apoptosis . In a separate study by the same group, an injectable thermo‐sensitive hydrogel based on a poly(ethylene glycol)‐poly(γ‐ethyl‐ l ‐glutamate) diblock copolymer (mPEG‐ b ‐PELG) was used to co‐deliver CDDP and IL‐15 for local treatment of melanoma . Animal studies on a B16F0‐RFP xenografted mouse model indicated that effector lymphocytes (CD8 + T cells and NK cells) could be activated and expanded with T reg suppression after peritumoral injection with the CDDP and IL‐15 co‐loaded hydrogel.…”

“…Animal studies on a B16F0‐RFP xenografted mouse model indicated that effector lymphocytes (CD8 + T cells and NK cells) could be activated and expanded with T reg suppression after peritumoral injection with the CDDP and IL‐15 co‐loaded hydrogel. Single treatment with the CDDP and IL‐15 co‐loaded hydrogel displayed markedly enhanced antitumor efficacy against melanoma when compared to treatment with a combination of free drugs or with the hydrogel containing CDDP or IL‐15 only …”

“…[80] To address the above challenges, several injectable hydrogel-based depot systems have been designed to co-deliver chemotherapeutics and immunotherapeutics for localized combination cancer therapy. [25,46,[81][82][83] The combination delivery systems are expected to not only maintain effective drug concentrations by prolonging the drug residence time at the tumor site, but also protect bioactive molecules against denaturation or degradation. [16] Immunotherapy agents were primarily loaded in the hydrogel by a physical embedding approach to protect their natural antitumor properties ( Table 2).…”

“…[83] In a separate study by the same group, an injectable thermo-sensitive hydrogel based on a poly(ethylene glycol)poly(γ-ethyl-l-glutamate) diblock copolymer (mPEG-b-PELG) was used to co-deliver CDDP and IL-15 for local treatment of melanoma. [81] Animal studies on a B16F0-RFP xenografted mouse model indicated that effector lymphocytes (CD8 + T cells and NK cells) could be activated and expanded with T reg suppression after peritumoral injection with the CDDP and IL-15 co-loaded hydrogel. Single treatment with the CDDP and IL-15 co-loaded hydrogel displayed markedly enhanced antitumor efficacy against melanoma when compared to treatment with a combination of free drugs or with the hydrogel containing CDDP or IL-15 only.…”