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PubMed2004

A novel approach for cancer immunotherapy: tumor cells with anchored superantigen SEA generate effective antitumor immunity.

Murine B16 melanoma cell line is poorly immunogenic and highly aggressive. We recently reported that the transmembrane staphylococcal enterotoxin A (TM-SEA) anchors onto B16 cells and stimulates lymphocyte proliferation. The purpose of the study was to investigate whether vaccination with B16 cells bearing membrane-anchored TM-SEA fusion protein could cause tumor-specific immunity. Mice in the therapeutic vaccination group received B16 tumor inoculations, followed by treatment with B16-TM-SEA vaccine or control vaccines. Mice in the prophylactic vaccination group were given B16-TM-SEA vaccine or control vaccines, followed by challenge with wild type B16 or control EL4 cells. Significant tumor growth inhibition, prolongation of survival, and marked augmentation of NK and CTL activities were observed in mice which received B16-TM-SEA vaccine as compared to controls. Overall, our results suggest that the TM-SEA cellular vaccine is a novel and effective strategy for cancer immunotherapy.

Animals↗
PubMed2006

Vascular endothelial growth factor blockade reduces intratumoral regulatory T cells and enhances the efficacy of a GM-CSF-secreting cancer immunotherapy.

PURPOSE: The purpose of the present study was to evaluate granulocyte macrophage colony-stimulating factor (GM-CSF)-secreting tumor cell immunotherapy in combination with vascular endothelial growth factor (VEGF) blockage in preclinical models. EXPERIMENTAL DESIGN: Survival and immune response were monitored in the B16 melanoma and the CT26 colon carcinoma models. VEGF blockade was achieved by using a recombinant adeno-associated virus vector expressing a soluble VEGF receptor consisting of selected domains of the VEGF receptors 1 and 2 (termed sVEGFR1/R2). Dendritic cell and tumor infiltrating lymphocyte activation status and numbers were evaluated by fluorescence-activated cell sorting analysis. Regulatory T cells were quantified by their CD4+CD25hi and CD4+FoxP3+ phenotype. RESULTS: The present study established that GM-CSF-secreting tumor cell immunotherapy with VEGF blockade significantly prolonged the survival of tumor-bearing mice. Enhanced anti-tumor protection correlated with an increased number of activated CD4+ and CD8+ tumor-infiltrating T cells and a pronounced decrease in the number of suppressive regulatory T cells residing in the tumor. Conversely, overexpression of VEGF from tumors resulted in elevated numbers of regulatory T cells in the tumor, suggesting a novel mechanism of VEGF-mediated immune suppression at the tumor site. CONCLUSION: GM-CSF-secreting cancer immunotherapy and VEGF blockade increases the i.t. ratio of effector to regulatory T cells to provide enhanced antitumor responses. This therapeutic combination may prove to be an effective strategy for the treatment of patients with cancer.

Animals↗
PubMed2004

Progress in head and neck cancer immunotherapy: can tolerance and immune suppression be reversed?

The incidence of squamous cell carcinoma of the head and neck (SCCHN) is greater than 40,000 cases per year in the United States, and approximately 500,000 cases annually worldwide. Despite significant advances in detection, ablation, and reconstruction, survival has not improved appreciably over the past few decades. Therefore, novel approaches are necessary to provide head and neck oncologists with a more effective armamentarium against this challenging disease. Cancer immunotherapy describes various approaches to expand and activate the immune system to control tumor growth in vivo. So far, immunotherapy appears to have had applicability in conjunction with other therapeutic interventions that treat residual tumor cells after therapy or to reduce the occurrence of second primary tumors. In particular, diseases such as SCCHN are attractive candidates for novel therapeutic approaches, since the standard treatments have not yet successfully controlled this disease with sufficiently high success rates. This article reviews adjuvant immunotherapeutic strategies currently in trials or under development for SCCHN patients, including vaccination or cytokine immunostimulation.

Adjuvants, Immunologic↗
PubMed2005

Dendritic cell-derived exosomes in cancer immunotherapy: exploiting nature's antigen delivery pathway.

Dendritic cells release large quantities of exosomes, known as dexosomes. These dexosomes are heat-stable, small vesicles (60-90 nm in diameter) made up of a lipid bilayer displaying an enrichment in sphingomyelin and a decrease in phosphatidylcholine content with no measurable asymmetry. They incorporate a characteristic set of proteins, including a large quantity of tetraspanins such as CD9 and CD81, all the known antigen presenting molecules (major histocompatibility complex class I and II, CD1 a, b, c and d) and the costimulatory molecule CD86. The function of dexosomes is to transfer antigen-loaded major histocompatibility complex class I and II molecules, and other associated molecules, to naive dendritic cells, potentially leading to the amplification of the cellular immune response. In preclinical mouse models, antigen-loaded dexosomes elicit strong antitumor activity. Human dexosomes can be prepared ex vivo relatively easily from dendritic cells derived from monocytes isolated by leukapheresis of healthy individuals or cancer patients. The feasibility of using dexosomes as a cancer therapeutic vaccine has been tested in two Phase I clinical studies in melanoma and lung cancer patients, respectively. These studies demonstrate that dexosomes can be prepared from cancer patient blood cells and be safely administered. Clinical observations suggested that dexosomes can stimulate both the adaptive (T-cells) and innate (natural killer cells) cellular immune responses. This review focuses on the perspective of using dexosomes in cancer immunotherapy. Concepts for using the exosome pathway in other possible pharmacologic applications are also discussed.

Antigens, Neoplasm↗
PubMed2002

Specific and effective targeting cancer immunotherapy with a combination of three bispecific antibodies.

For the purpose of establishing a new adoptive immunotherapy for bile duct carcinoma (BDC), we previously constructed two kinds of bispecific antibodies (bsAbs), anti-MUC1 x anti-CD3 (M x 3) and anti-MUC1 x anti-CD28 (M x 28), which activate T cells and form bridges between them and MUC1-expressing tumor cells. In our previous studies [Cancer Res. 56 (1996) 4205] specific targeting therapy (STT) consisting of i.v. administration of lymphokine activated killer cells with a T cell phenotype (T-LAK) sensitized with two kinds of bsAbs to human BDC-grafted severe combined immunodeficient (SCID) mice demonstrated remarkable inhibition of tumor growth. However, complete cures could not be obtained. In order to improve antitumor efficacy, we have paid attention to anti-CD2 monoclonal antibodies (mAbs), thought to play an important roles in signal transduction in T cell activation or control of T cell receptor (TCR)-driven activation. Therefore, we developed another bsAb, anti-MUC1 x anti-CD2 (M x 2), in order to examine if this would show synergism with the two previously described bsAbs. The combination of the three bsAbs (M x 3, M x 28 and M x 2 bsAbs) showed highest cytotoxicity against MUC1-expressing BDC cells when given simultaneously with peripheral blood mononuclear cells (PBMCs) or T-LAK cells in vitro. When 2 x 10(7) T-LAK cells sensitized with different combinations of bsAbs were administered four times i.v. to BDC-grafted SCID mice, the best therapeutic result was obtained with a combination of all three bsAbs. These results indicate usefulness of combination of three bsAbs for targeting cancer immunotherapy.

Animals↗
PubMed2003

Monitoring of circulating angiogenic factors in dendritic cell-based cancer immunotherapy.

BACKGROUND: A promising treatment approach for patients with malignant disease that recently has found its way into clinical trials is based on vaccination with autologous dendritic cells loaded with tumor antigens. However, adequate assays for monitoring clinical and immunologic responses still are under debate. In recent years, the determination of angiogenic markers has shown considerable potential in the diagnosis and prognosis of patients with malignant disease, because tumor growth and spread are promoted by angiogenesis, the formation of new blood vessels. METHODS: The authors established a method for measuring the plasma levels of three modulators of angiogenesis: vascular endothelial growth factor, platelet-derived endothelial cell growth factor, and thrombospondin-1. The angiogenic blood profile of a healthy control group was characterized and compared with a group of patients with malignant disease. Ultimately, levels of circulating angiogenic factors were monitored in the course of dendritic cell-based cancer immunotherapy. RESULTS: Baseline levels of angiogenic mediators varied substantially among healthy individuals but showed consistent values for each individual. Blood levels of circulating angiogenic factors were elevated significantly in patients with advanced disease and were highly sensitive to dendritic cell-based immunotherapy. CONCLUSIONS: To our knowledge, the current report was the first to analyze circulating levels of angiogenic factors during dendritic cell-based immunotherapy. The authors observed a noteworthy change in the angiogenic blood profile with treatment, and this change was correlated with the induction of an immunologic response.

Adult↗
PubMed2002

Immunoregulatory T cells in cancer immunotherapy.

Many of the tumour antigens targeted by active immunisation strategies are in fact self-antigens. Successful anticancer immunotherapy will therefore require not only potent methods of T cell activation, but also successful interference with mechanisms of immune tolerance that have evolved to prevent tissue destruction by autoreactive T cells. In addition to thymic deletion, anergy and skewing of T cell cytokine expression, a role for immunoregulatory T cells in the maintenance of self-tolerance has been suggested. Suppression of autoreactive T cells by regulatory T cells has been suggested to occur by both cytokine and cell-contact-dependent mechanisms. In murine models, suppression of auto-reactive T cells mediated by cell contact has been attributed to a population of spontaneously occurring CD4+CD25+ T cells. Cells with similar phenotype and function have been found in healthy humans. In murine models, these cells behave as regulatory T cells, counteracting autoimmune and inflammatory reactions, and have a role in tolerance and in peripheral T cell homeostasis. Of interest for cancer immunotherapy is the fact that depleting these cells results in the induction of antitumour immune responses, particularly after tumour specific vaccination. One hypothesis is that depleting these CD4+CD25+ counter-regulatory T cells in humans with cancer will enhance the efficacy of anticancer immunisations.

Animals↗
PubMed2002

Tissue distribution of target antigen has a decisive influence on the outcome of adoptive cancer immunotherapy.

Adoptive transfer of allogeneic T cells has unmatched efficacy to eradicate leukemic cells. We therefore sought to evaluate in kinetic terms interactions between T cells and allogeneic leukemic cells. T cells primed against the model B6(dom1) minor histocompatibility antigen were adoptively transferred in irradiated B10 (B6(dom1)-positive) and congenic B10.H7(b) (B6(dom1)-negative) recipients, some of which were also injected with EL4 leukemia/lymphoma cells (B6(dom1)-positive). A key finding was that the tissue distribution of the target epitope dramatically influenced the outcome of adoptive cancer immunotherapy. Widespread expression of B6(dom1) in B10 recipients induced apoptosis and dysfunction of antigen-specific T cells. Furthermore, in leukemic B10 and B10.H7(b) hosts, a massive accumulation of effector/memory B6(dom1)-specific T cells was detected in the bone marrow, the main site of EL4 cell growth. The accumulation of effector/memory cells in recipient bone marrow was EL4 dependent, and its kinetics was different from that observed in recipient spleen. We conclude that strategies must be devised to prevent apoptosis of adoptively transferred T cells confronted with a high antigen load and that local monitoring of the immune response at the site of tumor growth may be mandatory for a meaningful assessment of the efficacy of adoptive immunotherapy.

Animals↗
PubMed2002

Telomerase as a universal tumor-associated antigen for cancer immunotherapy.

Although the search for pharmacologic inhibitors of telomerase activity represents a promising approach for telomerase-based anti-cancer therapy, the immunological properties of the telomerase reverse transcriptase hTERT suggest that the enzyme is also an attractive target for novel immunotherapies against cancer. Data from both human and murine systems demonstrate that cytotoxic T-lymphocytes (CTL) can recognize peptides derived from TERT and kill TERT-positive tumor cells of multiple histologies. Given the vast overexpression of hTERT in human tumors and its low-level expression in rare normal tissues, clinical trials have begun that test the credentials of hTERT as a broadly applicable target for immunotherapy of cancer.

Antigens, Neoplasm↗
PubMed2003

Allogeneic immune replacement as cancer immunotherapy.

The graft-versus-leukaemia (GVL) reaction that occurs after allogeneic haematopoietic cell transplantation (HCT) can cure patients with a variety of haematological malignancies. A heightened appreciation of the GVL effect has resulted in the development of reduced intensity transplant approaches, where antitumour effects occur predominantly as a consequence of the transplanted donor immune system. The recent success of these transplants in patients with acute and chronic leukaemias has led to trials investigating for graft-versus-tumour (GVT) effects in patients with treatment-refractory metastatic solid tumours. This review discusses evidence that immune replacement following allogeneic HCT is a potent form of cancer immunotherapy for patients with haematological and non-haematological malignancies.

Animals↗
PubMed1992

Shi-quan-da-bu-tang (ten significant tonic decoction), SQT. A potent Chinese biological response modifier in cancer immunotherapy, potentiation and detoxification of anticancer drugs.

Shi-Quan-Da-Bu-Tang (Ten Significant Tonic Decoction), or SQT (Juzentaihoto, TJ-48) was formulated by Taiping Hui-Min Ju (Public Welfare Pharmacy Bureau) in Chinese Song Dynasty in AD 1200. It is prepared by extracting a mixture of ten medical herbs (Rehmannia glutinosa, Paeonia lactiflora, Liqusticum wallichii, Angelica sinesis, Glycyrrhiza uralensis, Poria cocos, Atractylodes macrocephala, Panax ginseng. Astragalus membranaceus and Cinnamomum cassia) that tone the blood and vital energy, and strengthen health and immunity. This potent and popular prescription has traditionally been used against anemia, anorexia, extreme exhaustion, fatigue, kidney and spleen insufficiency and general weakness, particularly after illness. In order to restore immunity in cancer patients, potentiate the therapeutic effect and ameliorate adverse toxicity of anticancer agents, 116 Chinese herbal formularies (Kampo) have been screened and evaluated. Fifteen compounds were found to have such actions. Among these, SQT was selected as the most effective as a potent biological response modifier. During the last eight years, animal models and clinical studies have revealed that SQT demonstrates extremely low toxicity (LD50 > 15 g/kg op murine), self-regulatory and synergistic actions of its components in immunomodulatory and immunopotentiating effects (by stimulating hemopoietic factors and interleukins production in association with NK cells, etc.), potentiates therapeutic activity in chemotherapy (mitomycin, cisplatin, cyclophosphamide and fluorouracil) and radiotherapy, inhibits the recurrence of malignancies, prolongs survival, as well as ameliorate and/or prevents adverse toxicities (GI disturbances such as anorexia, nausea, vomiting, hematotoxicity, immunosuppression, leukopenia, thrombocytopenia, anemia and nephropathy, etc.) of many anticancer drugs. The application and mechanistic studies of SQT in future development have potential importance in basic and clinical research of the traditional Chinese therapeutic approach of "toning the blood and strengthening Qi (vital energy)" in cancer immunotherapy.

Animals↗
PubMed2026

Miniature and versatile genome regulation TnpB-ωRNA toolkits facilitate cancer immunotherapy.

CRISPR‒Cas systems represent powerful tools for genome regulation. However, the large size of Cas proteins limits their efficient delivery via an adeno-associated virus (AAV), thereby restricting their clinical translation. Here, we engineer the IS200/IS605 transposon-encoded nuclease TnpB, along with its ωRNA scaffold, to create an enhanced TnpB system, which serves as a compact toolkit for gene activation, genome editing, and base editing. The gene activator enTnpBa increases expression by 2889-fold with a minimized 93 nt ωRNA and robustly activates endogenous genes in mammalian cells. We develop a single-AAV-based regimen for immune activation (AAV-ImmunAct) that delivers enTnpBa to activate CXCL9, IL-15, and IFN-γ. AAV-ImmunAct effectively enhances T cell migration and activation, increases killing of cancer cell lines and patient-derived organoids, and synergizes with anti-PD-1 therapy in humanized mice. Here, we establish enTnpB as a compact and versatile platform for genome regulation and a promising tool for cancer immunotherapy.

Humans↗
PubMed2001

Gene transfer of antisense hypoxia inducible factor-1 alpha enhances the therapeutic efficacy of cancer immunotherapy.

Solid tumors meet their demands for nascent blood vessels and increased glycolysis, to combat hypoxia, by activating multiple genes involved in angiogenesis and glucose metabolism. Hypoxia inducible factor-1 (HIF-1) is a constitutively expressed basic helix-loop-helix transcription factor, formed by the assembly of HIF-1alpha and HIF-1beta (Arnt), that is stablized in response to hypoxia, and rapidly degraded under normoxic conditions. It activates the transcription of genes important for maintaining oxygen homeostasis. Here, we demonstrate that engineered down-regulation of HIF-1alpha by intratumoral gene transfer of an antisense HIF-1alpha plasmid leads to the down-regulation of VEGF, and decreased tumor microvessel density. Antisense HIF-1alpha monotherapy resulted in the complete and permanent rejection of small (0.1 cm in diameter) EL-4 tumors, which is unusual for an anti-angiogenic agent where transient suppression of tumor growth is the norm. It induced NK cell-dependent rejection of tumors, but failed to stimulate systemic T cell-mediated anti-tumor immunity, and synergized with B7-1-mediated immunotherapy to cause the NK cell and CD8 T cell-dependent rejection of larger EL-4 tumors (0.4 cm in diameter) that were refractory to monotherapies. Mice cured of their tumors by combination therapy resisted a rechallenge with parental tumor cells, indicating systemic antitumor immunity had been achieved. In summary, whilst intensive investigations are in progress to target the many HIF-1 effectors, the results herein indicate that blocking hypoxia-inducible pathways and enhancing NK-mediated antitumor immunity by targeting HIF-1 itself may be advantageous, especially when combined with cancer immunotherapy.

Animals↗
PubMed2005

Tumor-dendritic cell fusion as a basis for cancer immunotherapy.

OBJECTIVE: To establish the basis for use of allogeneic dendritic-tumor fusion cells. STUDY DESIGN: Fusion cells were created by electrofusion. We used 2 allogeneic murine tumor lines (D5 and 4T1) that were virally transduced to express the antigen (beta-galactosidase) as a surrogate tumor marker. RESULTS: Cross-immunization was achieved with irradiated allogenic tumor cells. Successful electrofusion of dendritic cells and tumor cells was confirmed by using fluorescence-activated cell sorting and cytospin. Significant responses were shown in immunized mice against tumor challenge and established 3-day pulmonary metastasis with fusion cells. CONCLUSIONS: Allogeneic tumor sharing a common tumor antigen can immunize against syngeneic tumor challenge. Fusion cells showed successful immunization against tumor challenge and showed regression of 3-day established pulmonary metastasis. SIGNIFICANCE: These preclinical studies provide evidence that an allogenic tumor-dendritic cell fusion vaccine is a valid approach for head and neck cancer immunotherapy.

Animals↗
PubMed2005

The alpha-gal epitope and the anti-Gal antibody in xenotransplantation and in cancer immunotherapy.

The alpha-gal epitope (Galalpha1-3Galbeta1-(3)4GlcNAc-R) is abundantly synthesized on glycolipids and glycoproteins of non-primate mammals and New World monkeys by the glycosylation enzyme alpha1,3galactosyltransferase (alpha1,3GT). In humans, apes and Old World monkeys, this epitope is absent because the alpha1,3GT gene was inactivated in ancestral Old World primates. Instead, humans, apes and Old World monkeys produce the anti-Gal antibody, which specifically interacts with alpha-gal epitopes and which constitutes approximately 1% of circulating immunoglobulins. Anti-Gal has functioned as an immunological barrier, preventing the transplantation of pig organs into humans, because anti-Gal binds to the alpha-gal epitopes expressed on pig cells. The recent generation of alpha1,3GT knockout pigs that lack alpha-gal epitopes has resulted in the elimination of this immunological barrier. Anti-Gal can be exploited for clinical use in cancer immunotherapy by targeting autologous tumour vaccines to APC, thereby increasing their immunogenicity. Autologous intact tumour cells from haematological malignancies, or autologous tumour cell membranes from solid tumours are processed to express alpha-gal epitopes by incubation with neuraminidase, recombinant alpha1,3GT and with uridine diphosphate galactose. Subsequent immunization with such autologous tumour vaccines results in in vivo opsonization by anti-Gal IgG binding to these alpha-gal epitopes. The interaction of the Fc portion of the vaccine-bound anti-Gal with Fcgamma receptors of APC induces effective uptake of the vaccinating tumour cell membranes by the APC, followed by effective transport of the vaccinating tumour membranes to the regional lymph nodes, and processing and presentation of the tumour-associated antigen (TAA) peptides. Activation of tumour-specific T cells within the lymph nodes by autologous TAA peptides may elicit an immune response that in some patients will be potent enough to eradicate the residual tumour cells that remain after completion of standard therapy. A similar expression of alpha-gal epitopes can be achieved by transduction of tumour cells with an adenovirus vector (or other vectors) containing the alpha1,3GT gene, thus enabling anti-Gal-mediated targeting of the vaccinating transduced cells to APC. Intratumoral delivery of the alpha1,3GT gene by various vectors results in the expression of alpha-gal epitopes. Such expression of the xenograft carbohydrate phenotype is likely to induce anti-Gal-mediated destruction of the tumour lesion, similar to rejection of xenografts by this antibody. Opsonization of the destroyed tumour cell membranes by anti-Gal IgG further targets them to APC, thus converting the tumour lesion, treated by the alpha1,3GT gene, into an in situ autologous tumour vaccine.

Animals↗
PubMedDate not supplied

CD8+ T cell tolerance and cancer immunotherapy.

To provide protection against all foreign pathogens one can possibly encounter during their lifetime, the T cell repertoire has to be as diverse as possible. At the same time, it is desirable that the T cell repertoire remains unresponsive towards healthy tissues. To realize this self/nonself discriminatory property, T cells undergo tightly controlled selection processes during maturation in the thymus. The key parameter determining the outcome of these selection processes is the avidity of the T cells for self-MHC/self-peptide complexes expressed in the thymus; low avidity interactions result in positive selection, whereas high avidity interactions lead to negative selection. Despite the selection processes, self-tolerance is far from absolute. In many cases, this is due to the presence of self-antigen in the thymus at a level that is too low to induce thymic deletion. In addition, T cells with a low avidity for ubiquitously expressed self-antigens can escape clonal deletion and enter the periphery. A thorough understanding of the self-specific T cell repertoire is important because many potential targets for cancer immunotherapy are self-proteins. In this review, the authors discuss the impact of self-antigen expression on the CD8+ T cell repertoire. An overview of the fate and functional capacities of self-specific T cells with specificity for tissue-restricted self-antigens and for ubiquitously expressed self-antigens is provided. Furthermore, the authors discuss the influence of negative selection on the antitumor reactivity of the mature T cell repertoire.

Animals↗
PubMed2000

Cancer immunotherapy using dendritic cell-derived exosomes.

Dendritic cells (DCs) are the most potent antigen presenting cells and the only ones capable of inducing primary cytotoxic immune responses. We found that DCs secrete a population of membrane vesicles, called exosomes. Exosomes are 60-80 nm vesicles of endocytic origin. The protein composition of exosomes was subjected to a systematic proteomic analysis. Besides MHC and co-stimulatory molecules, exosomes bear several adhesion proteins, most likely involved in their specific subjected to targeting. We also found that exosomes accumulate several cytosolic factors, probably involved in their endosomal biogenesis. Like DCs, exosomes induced immune responses in vivo. Indeed, a single injection of DC-derived exosomes sensitized with tumor peptides induced potent anti tumor immune responses in mice and the eradication of established tumors. Tumor-specific cytotoxic T lymphocytes were found in the spleen of exosome-treated mice, and the anti tumor effect of exosomes was sensitive to in vivo depletion of CD8+ T cells. These results show that exosomes induce potent anti tumor effects in vivo, and strongly support the implementation of human DC-derived exosomes for cancer immunotherapy.

Animals↗
PubMed2025

Fluorinated Ionizable Lipids for Efficient Spleen-Targeted mRNA Delivery in Cancer Immunotherapy.

Efficient and selective mRNA delivery to immune-related organs, particularly the spleen, remains a major barrier to the broader clinical translation of mRNA therapeutics. Here, leveraging the clinically approved SM-102/ALC-0315 ionizable lipid scaffold, we rationally designed a combinatorial library of fluorinated ionizable lipids (FILs) by systematically modulating hydrophobic tails and fluorine stoichiometry. Through synthesis and evaluation of 74 candidate FILs, we identify SSC6F5 lipid nanoparticles (LNPs) as a lead formulation with exceptional spleen-targeting specificity (>90%) across intravenous, intramuscular, and subcutaneous administrations. Compared to clinically approved SM102 LNPs and spleen-tropic SM102/18PA (SORT) LNPs, intravenously administered SSC6F5 LNPs achieve 10.6-fold and 63.1-fold higher splenic mRNA transfection, respectively. Proteomic analysis of protein corona on SSC6F5 LNPs reveals significant enrichment of apolipoprotein D (Apod) and reduction in apolipoprotein H (Apoh), implicating a novel endogenous recognition pathway driving enhanced spleen targeting. Functionally, SSC6F5 LNPs enable efficient genome editing in splenic macrophages, dendritic cells, T cells, and B cells in Ai9 mice, and elicit potent CD8+ T cell and humoral responses in a B16-OVA murine melanoma model, resulting in significant tumor growth inhibition. These findings establish fluorinated lipids as a mechanistically distinct and translationally versatile platform for precision spleen-targeted mRNA delivery in gene editing and cancer immunotherapy.

Animals↗