Combination of TLR9 agonists EnanDIM with checkpoint inhibitors for cancer immunotherapy.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 134-134
Author(s):  
Manuel Schmidt ◽  
Kerstin Kapp ◽  
Detlef Oswald ◽  
Burghardt Wittig ◽  
Barbara Volz
Keyword(s):  
Immune System ◽  
Tumor Growth ◽  
Colon Carcinoma ◽  
Mononuclear Cells ◽  
Checkpoint Inhibitors ◽  
Tumor Model ◽  
Tumor Growth Inhibition ◽  
Mouse Tumor ◽  
New Family ◽  
Ifn Alpha

134 Background: TLR9 agonists have shown anti-tumor effects by modulating the innate and adaptive immune system. Ongoing clinical studies support the use of TLR9 agonists for immunotherapeutic approaches. The new family of TLR9 agonists, EnanDIM, consists of linear single-stranded ODN synthesized using L-deoxyribonucleotides (natural enantiomers of D-deoxyribonucleotides) at their 3’-ends to prevent degradation. Therefore, EnanDIM does not own the off-target effects of PTO-modified CpG-ODN. Methods: EnanDIM with varying nucleotid sequences were compared for IFN-alpha response from human peripheral blood mononuclear cells and those molecules inducing the stronges response were selected. A maximum feasible dose (MFD) approach was employed to evaluate their acute toxicity and immunomodulatory properties. In addition, a combinatory approach with aPD-1 was evaluated in an syngeneic colon carcinoma CT26 mouse tumor model. Results: EnanDIM581 and EnanDIM532 were selected due to their pronounced activation of the IFN-alpha pathway in vitro. Safety assessments throughout and a gross necropsy at the end of the study revealed no signs of toxicity despite extremely high doses (300 - 1700 mg/kg). Dose-dependent increase of IP-10 levels in serum was observed between 6 and 24 hours after injection. In the colon carcinoma CT26 model subcutaneous injection of EnanDIM532 and intraperitoneal injection of aPD-1 had a moderate effect on the tumor growth when used in monotherapy (28.3% and 57.0% tumor growth inhibition, TGI). Notably, a combination of EnanDIM532 and aPD-1 further reduced tumor growth (74.7% TGI) and thus prolonged survival of the mice. Conclusions: In conclusion, EnanDIM, a new family of TLR9 agonists and immune surveillance reactivators (ISR), broadly activates the immune system, shows no toxicity in an MFD study and enhances the anti-tumor effects of the aPD-1 checkpoint inhibitor in a pilot study of a murine colon carcinoma tumor model. These data show the promising potential of EnanDIM not only for monotherapeutic but also combinatory approaches.

Combination of TLR9 agonist lefitolimod/MGN1703 with checkpoint inhibitors for cancer immunotherapy.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 634-634 ◽  
Author(s):  
Manuel Schmidt ◽  
Kerstin Kapp ◽  
Barbara Volz ◽  
Detlef Oswald ◽  
Burghardt Wittig
Keyword(s):  
Tumor Growth ◽  
Colon Carcinoma ◽  
Checkpoint Inhibitors ◽  
Immune Surveillance ◽  
Phase Iii ◽  
Tumor Growth Inhibition ◽  
Tumor Models ◽  
Pilot Studies ◽  
Murine Tumor

634 Background: TLR9 agonists are potent activators of the immune system via induction of cellular and humoral responses. Preclinical and ongoing clinical studies support the use of TLR9 agonists for immunotherapeutic approaches. Lefitolimod/MGN1703 is a covalently-closed dumbbell-like immune surveillance reactivator (ISR) with a broad immunomodulatory potential. After promising data from a phase II trial (IMPACT) as maintenance therapy after first-line induction chemotherapy in patients with metastatic colorectal cancer lefitolimod is recently evaluated in a phase III trial in mCRC patients (IMPALA). Methods: It was previously shown that lefitolimod can reduce tumor growth in several murine tumor models. Since the mode-of-action of lefitolimod starts upstream of the initiation points of checkpoint inhibitors aCTLA-4 or aPD-1/aPD-L1 a combinatory approach may result in an enhanced anti-tumor effect. Therefore, we employed two syngeneic murine tumor models: One with s.c. inoculation of CT26 cells and another with s.c. A20 cell challenge. Multiple doses of lefitolimod were injected s.c. or i.tu. Results: In the colon carcinoma CT26 model i.p. injection of aPD-L1 had no effect on the tumor growth, whereas peritumoral injection of lefitolimod led to a slowed tumor growth. The tumor growth was further inhibited by the combination (tumor growth inhibition, TGI - aPD-L1: no, lefitolimod: 28%, combination: 48%) resulting in prolonged survival of the mice. This combinatory effect was even more pronounced in the lymphoma A20 model: Injections of anti-PD-1 (i.p.) or lefitolimod (i.tu.) alone had a moderate anti-tumor effect which was vastly increased by the combination (TGI - aPD-1: 46%, lefitolimod: 50%, combination: 99%). Conclusions: In conclusion, we showed that lefitolimod, a member of dSLIM family of TLR9 agonists and an ISR, can enhance the limited anti-tumor effects of checkpoint inhibitors in pilot studies in murine colon carcinoma and lymphoma tumor models in vivo. These data show the promising potential for the combination with checkpoint inhibitors. In fact, a clinical trial in cooperation with MD Anderson evaluating the benefit of lefitolimod in combination with ipilimumab is currently ongoing.

TLR9 agonist lefitolimod to improve antitumor effect of checkpoint inhibitors in vivo.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14625-e14625 ◽  
Author(s):  
Manuel Schmidt ◽  
Kerstin Kapp ◽  
Barbara Volz ◽  
Detlef Oswald ◽  
Burghardt Wittig
Keyword(s):  
Tumor Growth ◽  
Colon Carcinoma ◽  
Checkpoint Inhibitors ◽  
Phase 1 ◽  
Tumor Growth Inhibition ◽  
Phase 2 ◽  
Tumor Models ◽  
Pilot Studies ◽  
Phase 2 Trial

e14625 Background: TLR9 agonists are potent activators of the immune system via induction of cellular and humoral responses. Preclinical and ongoing clinical studies support the use of TLR9 agonists for immunotherapeutic approaches. Lefitolimod/MGN1703 is a covalently-closed dumbbell-like immune surveillance reactivator (ISR) with a broad immunomodulatory potential. Due to promising data from a phase 2 trial (IMPACT) as maintenance therapy after first-line chemotherapy in mCRC patients lefitolimod is recently evaluated in a phase 3 trial in mCRC patients (IMPALA). Furthermore, lefitolimod is currently investigated in a phase 2 trial in SCLC patients (IMPULSE) and in a phase 1 / 2 trial in HIV patients (TEACH). Methods: It was shown that lefitolimod reduces tumor growth in several murine tumor models. Since the mode-of-action of lefitolimod starts upstream of the initiation points of checkpoint inhibitors like anti-CTLA-4 or anti-PD-1/anti-PD-L1 a combinatory approach may result in an enhanced anti-tumor effect. Therefore, two syngeneic murine models were used – a colon carcinoma CT26 and a lymphoma A20 model – for evaluation of the anti-tumor effect in vivo. Results: In the CT26 model treatment with anti-PD-L1 (i.p.) had no effect on the tumor growth, whereas addition of lefitolimod (s.c.) to anti-PD-L1 led to an anti-tumor effect (tumor growth inhibition, TGI 48%) which consequently resulted in prolonged survival of the mice. This combinatory effect was even more pronounced in the A20 model where treatment with anti-PD-1 (i.p.) alone had a moderate anti-tumor effect which was vastly increased by the combination (TGI – anti-PD-1: 46%, anti-PD-1/lefitolimod 99%). Conclusions: In conclusion, we showed that lefitolimod, a member of dSLIM® family of TLR9 agonists and an ISR, can enhance the limited anti-tumor effects of checkpoint inhibitors in pilot studies in murine colon carcinoma and lymphoma tumor models in vivo. These data show the promising potential for the combination with checkpoint inhibitors. Notably, a clinical trial in cooperation with MD Anderson evaluating the benefit of lefitolimod in combination with ipilimumab is currently ongoing.

scholarly journals Astragalus membranaceus–Derived Anti-Programmed Death-1 Monoclonal Antibodies with Immunomodulatory Therapeutic Effects against Tumors

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Fu-Ling Chang ◽  
Keng-Chang Tsai ◽  
Tsai-Yu Lin ◽  
Tz-Wen Yang ◽  
Yan-Ni Lo ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Growth Inhibition ◽  
Mononuclear Cells ◽  
Synergistic Effects ◽  
Astragalus Membranaceus ◽  
Tumor Growth Inhibition ◽  
Therapeutic Effects ◽  
Single Chain ◽  
Programmed Death ◽  
Programmed Death 1

Astragalus membranaceus polysaccharide (APS) components are main ingredients of TCM and have proven efficacy to activate T cells and B cells, enhancing immunity in humans. In this study, elevated cytokine and anti-PD-1 antibody titers were found in mice after immunization with APS. Therefore, phage-display technology was utilized to isolate specific anti-programmed death-1 (PD-1) antibodies from mice stimulated by APS and to confirm whether the isolated anti-PD-1 antibody could inhibit the interaction of PD-1 with the programmed death-ligand 1 (PD-L1), resulting in tumor growth inhibition. The isolated single-chain fragment variable (scFv) S12 exhibited the highest binding affinity of 20 nM to PD-1, completed the interaction between PD-1 and PD-L1, and blocked the effect of PD-L1-induced T cell exhaustion in peripheral blood mononuclear cells in vitro. In the animal model, the tumor growth inhibition effect after scFv S12 treatment was approximately 48%. However, meaningful synergistic effects were not observed when scFv S12 was used as a cotreatment with ixabepilone. Moreover, this treatment caused a reduction in the number of tumor-associated macrophages in the tumor tissue. These experimental results indirectly indicate the ability of APS to induce specific antibodies associated with the immune checkpoint system and the potential benefits for improving immunity in humans.

Anti-Tumor Activity of the Aurora a Inhibitor MLN8237 in Diffuse Large B-Cell Lymphoma Preclinical Models.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1592-1592 ◽  
Author(s):  
Jessica J Huck ◽  
Mengkun Zhang ◽  
Marc L Hyer ◽  
Mark G Manfredi
Keyword(s):  
Tumor Growth ◽  
Growth Inhibition ◽  
Tumor Model ◽  
B Cell Lymphoma ◽  
Tumor Growth Inhibition ◽  
Aurora A ◽  
Hct 116 ◽  
Xenograft Models

Abstract Aurora A kinase is a serine/threonine protein kinase that is essential for normal transit of cells through mitosis. In many tumor types the Aurora A gene is amplified and/or the protein is over-expressed. The Aurora A small-molecule inhibitor MLN8237 demonstrated robust tumor growth inhibition in xenograft models of solid tumors grown subcutaneously (S.C.) in immunocompromised mice. Here we explored the antitumor activity of MLN8237 in models of diffuse large B-cell lymphoma (DLBCL) both in vitro and in vivo. In vivo three established DLBCL xenograft models (OCI-Ly7, OCI-Ly19, and WSU-DLCL2; all cells expressing luciferase) and a primary DLBCL tumor model PHTX-22-06 were tested using MLN8237 at different doses. Rituximab, an anti-CD20 monoclonal antibody that is active against CD20+ malignant B cells and is a standard of care agent was used for comparison. Using these model systems, tumor cells were injected either I.V. (to evaluate disseminated disease), or S.C. in severe combined immunodeficient mice (SCID). Animals were dosed orally for 21 days with MLN8237 (QD or BID) at various doses, or Rituximab dosed at 10mg/kg IV (once/week) and tumor growth inhibition was monitored using either bioluminescent imaging for the disseminated models or vernier calipers for the S.C. models. Tumor growth inhibition by MLN8237 was dose dependent with 20 mg/kg bid being the most efficacious dose (TGI>100% in both disseminated OCI-Ly19 and WSU models). All animals in the OCI-Ly19 disseminated model 20 mg/kg BID treatment group demonstrated regressions and remained disease free until the end of the study, day 65. In this study the Rituximab treated animals were euthanized on day 31 due to a high level of tumor burden. In the primary tumor model, PHTX-22-06, MLN8237 dosed at 20 mg/kg BID was also the most efficacious with a TGI of 95%. Moreover, tumor growth inhibition was durable as determined by prolonged tumor growth delay (>50 days). Significant efficacy was achieved in all models tested, whether grown as disseminated or subcutaneous models. A noted increase in durability of response was observed with MLN8237 treatment when compared with previous data from solid tumor models. In vitro, MLN8237 treatment increased levels of apoptosis in the OCI-Ly19 cells in comparison to the solid tumor cell line HCT-116 (colon). Greater Annexin V positive cells and greater cleaved PARP and Caspase-3 signals were detected in the MLN8237 treated OCI-Ly19 cells when compared to HCT-116 cells. The demonstration of robust and durable anti-tumor activity in preclinical models treated with MLN8237 provides the basis for its clinical evaluation as a treatment option for DLBCL. MLN8237 is currently in multiple Phase I clinical trials.

scholarly journals Vascular disrupting agent induced aggregation of gold nanoparticles for photothermally enhanced tumor vascular disruption

2020 ◽  
Vol 6 (23) ◽  
pp. eabb0020 ◽  
Author(s):  
Sheng Hong ◽  
Di-Wei Zheng ◽  
Cheng Zhang ◽  
Qian-Xiao Huang ◽  
Si-Xue Cheng ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Tumor Growth ◽  
Tumor Therapy ◽  
Tumor Model ◽  
Vascular Damage ◽  
Photothermal Effect ◽  
Tumor Growth Inhibition ◽  
Vascular Disrupting Agent ◽  
Induced Aggregation ◽  
Vascular Disrupting

Although vascular disrupting agents (VDAs) have been extensively implemented in current clinical tumor therapy, the notable adverse events caused by long-term dosing severely limit the therapeutic efficacy. To improve this therapy, we report a strategy for VDA-induced aggregation of gold nanoparticles to further destroy tumor vascular by photothermal effect. This strategy could effectively disrupt tumor vascular and cut off the nutrition supply after just one treatment. In the murine tumor model, this strategy results in notable tumor growth inhibition and gives rise to a 92.7% suppression of tumor growth. Besides, enhanced vascular damage could also prevent cancer cells from distant metastasis. Moreover, compared with clinical therapies, this strategy still exhibits preferable tumor suppression and metastasis inhibition ability. These results indicate that this strategy has great potential in tumor treatment and could effectively enhance tumor vascular damage and avoid the side effects caused by frequent administration.

586 Intratumoral DNA-based gene transfer as an efficient delivery approach to combine checkpoint-inhibiting antibodies with interleukin 12

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A621-A621
Author(s):  
Liesl Jacobs ◽  
Elien De Smidt ◽  
Nick Geukens ◽  
Kevin Hollevoet ◽  
Paul Declerck
Keyword(s):  
Gene Transfer ◽  
Tumor Growth ◽  
Checkpoint Inhibitors ◽  
Tumor Model ◽  
Interleukin 12 ◽  
Individual Treatment ◽  
List Type ◽  
Triple Combination ◽  
Intratumoral Delivery ◽  
Abscopal Effects

BackgroundCheckpoint inhibitors have demonstrated clinical benefit for several types of cancer, but still a large proportion of patients do not respond to treatment. To improve response rates, many combination therapies are currently under clinical evaluation. One such example is the combination of anti-PD-1 monoclonal antibodies with intratumoral gene transfer of plasmid-based interleukin 12 (IL-12). Local expression of the cytokine IL-12 has been shown to increase immune cell infiltration in cold tumors, which can make them more responsive to anti-PD-1 antibodies.1 The current study evaluates the efficacy of simultaneous delivery of checkpoint-inhibiting antibodies and IL-12 by intratumoral gene transfer. We recently demonstrated that intratumoral delivery of plasmid-based checkpoint inhibitors yielded systemic anti-tumor responses in a mouse tumor model, with only limited systemic antibody exposure and therefore improved biosafety.2MethodsC57BL/6J mice bearing a subcutaneous syngeneic MC38 tumor received a single intratumoral injection of plasmid DNA followed by in vivo electroporation. DNA-based IL-12 (p(IL-12), 2.5 µg) was administered alone or in combination with a DNA-based anti-PD-1 antibody (p(aPD-1), 60 µg) and/or DNA-based anti-CTLA-4 antibody (p(aCTLA-4), 60 µg). Abscopal effects were studied in mice bearing two contralateral tumors, of which only one received therapy.ResultsThe combined intratumoral delivery of p(IL-12) and p(aPD-1) resulted in 10% complete responders, in contrast to no complete tumor regressions with each individual treatment. Yet, differences in tumor growth or survival did not reach statistical significance between these groups. To improve anti-tumor efficacy, the combined gene transfer was expanded with a second DNA-based checkpoint inhibitor, p(aCTLA-4). While intratumoral delivery of this triple combination also led to 10% complete regressions, the response did result in significant tumor growth delay compared to p(IL-12) alone (p<0.05) and the combination of both checkpoint inhibitors (p<0.01). Moreover, in a dual MC38 tumor model, the triple combination enabled significant abscopal effects compared to untreated mice (p<0.01), which was not the case for the other treatments.ConclusionsThis study demonstrates that intratumoral DNA-based gene transfer can be applied to efficiently combine different immunotherapeutics. This approach allows simplification of the treatment schedule, addresses the complex production of conventional protein-based therapeutics, and enables local drug expression, thereby minimizing systemic exposure and subsequent adverse events. Ongoing studies focus on the further validation of combined intratumoral delivery of plasmid-based checkpoint inhibitors and IL-12, by investigating the effect on tumor-infiltrating and peripheral immune cells as well as through evaluation of the triple combination in other tumor models.Ethics ApprovalThis study was approved by the KU Leuven Animal Ethics Committee, approval number P130/2017.ReferencesAlgazi AP, et al. Phase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma. Clin Cancer Res 2020; 26:2827–2837.Jacobs L, et al. DNA-based delivery of checkpoint inhibitors in muscle and tumor enables long-term responses with distinct exposure. Mol Ther 2020;28:1068–1077.

scholarly journals Antitumor effect ofBothrops jararacavenom

2002 ◽  
Vol 11 (2) ◽  
pp. 99-104 ◽  
Author(s):  
Reinaldo J. da Silva ◽  
Márcia G. da Silva ◽  
Lízia C. Vilela ◽  
Denise Fecchio
Keyword(s):  
Tumor Growth ◽  
Survival Time ◽  
Antitumor Effect ◽  
Mononuclear Cells ◽  
Experimental Studies ◽  
Tumor Growth Inhibition ◽  
Peritoneal Cells ◽  
Eat Cells

Many experimental studies have been carried out using snake venoms for the treatment of animal tumors, with controversial results. While some authors have reported an antitumor effect of treatment with specific snake venom fractions, others have reported no effects after this treatment. The aim of this study was to evaluate the effect ofBothrops jararacavenom (BjV) on Ehrlich ascites tumor (EAT) cellsin vivoandin vitro. In thein vivostudy, Swiss mice were inoculated with EAT cells by the intraperitoneal (i.p.) route and treated withBjV venom (0.4 mg/kg, i.p.), on the 1st, 4th, 7th, 10th, and 13th days. Mice were evaluated for total and differential cells number on the 2nd, 5th, 8th, 11th and 14th days. The survival time was also evaluated after 60 days of tumor growth. In thein vitrostudy, EAT and normal peritoneal cells were cultivated in the presence of differentBjV concentrations (2.5, 5.0, 10.0, 20.0, 40.0, and 80 μg) and viability was verified after 3, 6, 12 and 24 h of cultivation. Results were analyzed statistically by the Kruskal-Wallis and Tukey tests at the 5% level of significance. It was observed thatin vivotreatment withBjV induced tumor growth inhibition, increased animal survival time, decreased mortality, increased the influx of polymorphonuclear leukocytes on the early stages of tumor growth, and did not affect the mononuclear cells number.In vitrotreatment withBjV produced a dose-dependent toxic effect on EAT and peritoneal cells, with higher effects against peritoneal cells. Taken together, our results demonstrate thatBjV has an important antitumor effect. This is the first report showing thisin vivoeffect for this venom.

scholarly journals 276 Discovery and preclinical characterization of anti-LILRB2 antibodies that rescue T cells from macrophage-mediated immune suppression

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A299-A299
Author(s):  
Meghan Zuck ◽  
Huyen Dinh ◽  
Valerie Wall ◽  
Sam Lam ◽  
Ramya Chandrasekaran ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Suppression ◽  
Tumor Regression ◽  
Checkpoint Inhibitors ◽  
Myeloid Cells ◽  
Tumor Model ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tumor Growth Inhibition ◽  
Variable Regions

BackgroundThe inhibitory receptor leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2, ILT4), is expressed on immunosuppressive myeloid cells, and has emerged as a key immune checkpoint in the tumor microenvironment (TME). Interaction of LILRB2 with the HLA class I ligands (e.g., HLA-G, HLA-A, etc.) mediates immune suppression by myeloid cells and promotes tumor immune evasion. Targeting this pathway in the TME may enhance efficacy of T cell checkpoint inhibitors. Antibodies targeting LILRB2 are currently being evaluated in clinical trials for the treatment of cancer.MethodsAnti-LILRB2 antibodies were cloned from B cells derived from rabbits immunized with human LILRB2 recombinant protein. Cells were cultured at clonal density, and IgG antibodies in supernatants were evaluated for binding to human and cynomolgus LILRB2. Variable-regions from positive hits were sequenced, cloned, and expressed as recombinant rabbit-human chimeras. Anti-LILRB2 chimeric antibodies were evaluated in a panel of functional and phenotypic assays using primary human macrophages and T cells, and then prioritized for evaluation in a humanized NSG-SGM3 tumor model.ResultsTwenty-seven rabbit anti-LILRB2 clones were selected and expressed as rabbit-human IgG4 chimeras based on binding to recombinant human LILRB2 protein and blocking of HLA-G binding to LILRB2. A subset of chimeric clones demonstrated binding to stably expressing LILRB2 cells, and lack of binding to other LILRB or LILRA family members by enzyme-linked immunosorbent assay and by flow cytometry of transiently transfected HEK cells. Lead clones were identified based on their ability to block interaction of LILRB2 to HLA-G expressed on tumor cells, and activity in functional cell-based assays modeling LILRB2-mediated immune suppression. These clones enhanced LPS-induced IFN-γ production by PBMCs and increased the release of TNF-α by CD40L-activated macrophages. Selected clones also relieved M2c-macrophage-mediated immune suppression in a M2c/CD8+ T cell coculture assay by restoring T-cell proliferation and secretion of pro-inflammatory cytokines. Importantly, lead chimeric LILRB2 clones demonstrated in vivo efficacy with significant tumor growth inhibition and tumor regression in an SK-MEL-5 tumor model in humanized NSG-SGM3 mice.ConclusionsWe identified novel anti-LILRB2 antibodies that restore innate and adaptive immune responses by modulating immunosuppressive macrophages. These data provide a strong rationale for further development of these antibodies as an anti-cancer immunotherapy.

scholarly journals Antitumor efficiency of contact radiotherapy in combination with a chlorin-based photosensitizer in experiment

2021 ◽  
Vol 10 (2) ◽  
pp. 25-33
Author(s):  
D. A. Tzerkovsky ◽  
Ya. L. Protopovich ◽  
D. I. Kozlovsky ◽  
V. A. Suslova
Keyword(s):  
Radiation Therapy ◽  
Tumor Growth ◽  
Growth Inhibition ◽  
Tumor Model ◽  
Growth Patterns ◽  
Antitumor Efficacy ◽  
Laboratory Animals ◽  
Tumor Growth Inhibition ◽  
Histological Structure ◽  
Complete Tumor

Authors have studied the antitumor efficacy of contact radiation therapy (CRT) in combination with a chlorin-based photosensitizer (PS) in an experiment on laboratory animals with transplanted tumors. The experimental study was performed in 50 white outbred rats weighing 250±50 g. Subcutaneously transplanted Pliss lymphosarcoma (PLS) and alveolar liver cancer RS1 (RS1) were used as tumor models. Chlorinbased PS photolon (RUE «Belmedpreparaty», Republic Belarus) was injected intravenously at a dose of 2.5 mg/kg. The radiation sessions were carried out 2.5–4 hours (depending on the tumor model) after the administration of the PS using the device «microSelectron HDR V3 Digital» («Nucletron», Netherlands) with a 192-Ir radiation source in single focal doses 5 and 10 Gy. All laboratory animals (for PLS and RS1) were subdivided into 5 groups of 5 animals each: intact control, CRT 5 Gy, CRT 10 Gy, PS + CRT 5 Gy, PS + CRT 10 Gy. For the PLS tumor model – on the 14th day from the beginning of the experiment Vav. in groups were 26.31±5.81; 22.45±6.97; 18.99±4.86; 10.75±5.18 and 28.06±2.85 cm3, respectively (p˂0.05). The coefficients of tumor growth inhibition in the experimental groups were 14.67%, 27.82%, 59.14% and 6.65%, respectively. The frequency of complete tumor regressions 60 days after the start of the experiment was 0%, 20%, 20%, 60%, and 20%, respectively. On RS1 tumor model – on the 14th day from the beginning of the experiment Vav. in groups were 4.48±1.03; 0.80±0.21; 0.29±0.09; 0.19±0.07 and 0.32±0.08 cm3, respectively (p=0.009). The coefficients of tumor growth inhibition in the experimental groups were 82.14%, 93.53%, 95.76% and 92.86%, respectively. The frequency of complete tumor regressions 60 days after the start of the experiment was 0%, 0%, 20%, 0%, and 0%, respectively. Systemic administration of chlorin-based PS before the CRT session increases the antitumor efficacy of radiation therapy in animals with transplantable tumors of different histological structure and growth patterns. The data obtained indicate that further studies of the radiosensitizing properties of PS are promising.

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