Kojarzenie leków z grupy immunoterapii — skutki biologiczne i potencjalne korzyści
Streszczenie
Ze względu na ograniczoną skuteczność immunoterapii stosowanej w leczeniu I linii u chorych na niedrobnokomórkowego raka płuca powstały koncepcje łączenia klasycznej immunoterapii przeciwciałami przeciwko immunologicznym punktom kontroli (ICIs) z innymi metodami leczenia (chemioterapia, chemioradioterapia, immunoterapia). Z uwagi na stosunkowo niską toksyczność i wysoką efektywność wyjątkowo obiecujące są metody leczenia, w których stosuje się skojarzenie dwóch różnych metod immunoterapii. Takie postępowanie opiera się m.in. na obserwacjach z badań klinicznych, w których stosowano łącznie niwolumab i ipilimumab w terapii zaawansowanego czerniaka i niedrobnokomórkowego raka płuca. Okazało się, że podwójna blokada immunologicznych punktów kontrolnych aktywuje limfocyty T na różnych etapach formowania się swoistej odpowiedzi immunologicznej, jednocześnie wpływając na obniżenie aktywności immunologicznych komórek supresyjnych (limfocyty T regulatorowe). Eksperymenty te nie tylko zaowocowały rejestracją terapii skojarzonej z użyciem niwolumabu i ipilimumabu, ale także zainicjowały badania kliniczne, w których stosuje się przeciwciała przeciwko innym immunologicznym punktom kontrolnym w skojarzeniu ze znanymi ICIs. Prowadzone są też badania, w których kojarzy się ICIs z cząsteczkami modyfikującymi mikrośrodowisko nowotworowe oraz stymulującymi nieswoiście układ immunologiczny. W artykule opisano mechanizm synergistycznego działania skojarzenia różnych metod immunoterapii u chorych na nowotwory oraz potencjalne korzyści wynikające ze stosowania terapii skojarzonej.
Słowa kluczowe: immunoterapiaimmunologiczne punkty kontrolimikrośrodowisko nowotworowe
Referencje
- Esfahani K, Roudaia L, Buhlaiga N, et al. A review of cancer immunotherapy: from the past, to the present, to the future. Curr Oncol. 2020; 27(Suppl 2): S87–S97.
- Korman AJ, Peggs KS, Allison JP. Checkpoint blockade in cancer immunotherapy. Adv Immunol. 2006; 90: 297–339.
- Valecha GK, Vennepureddy A, Ibrahim U, et al. Anti-PD-1/PD-L1 antibodies in non-small cell lung cancer: the era of immunotherapy. Expert Rev Anticancer Ther. 2017; 17(1): 47–59.
- Hargadon KM, Johnson CE, Williams CJ. Immune checkpoint blockade therapy for cancer: An overview of FDA-approved immune checkpoint inhibitors. Int Immunopharmacol. 2018; 62: 29–39.
- Spencer KR, Wang J, Silk AW, et al. Biomarkers for Immunotherapy: Current Developments and Challenges. Am Soc Clin Oncol Educ Book. 2016; 35: e493–e503.
- Weber JS. Biomarkers for Checkpoint Inhibition. Am Soc Clin Oncol Educ Book. 2017; 37: 205–209.
- Zappasodi R, Merghoub T, Wolchok JD, et al. Emerging Concepts for Immune Checkpoint Blockade-Based Combination Therapies. Cancer Cell. 2018; 33(4): 581–598.
- Das R, Verma R, Sznol M, et al. Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo. J Immunol. 2015; 194(3): 950–959.
- Wei SC, Duffy CR, Allison JP. Fundamental Mechanisms of Immune Checkpoint Blockade Therapy. Cancer Discov. 2018; 8(9): 1069–1086.
- Wei SC, Levine JH, Cogdill AP, et al. Distinct Cellular Mechanisms Underlie Anti-CTLA-4 and Anti-PD-1 Checkpoint Blockade. Cell. 2017; 170(6): 1120–1133.e17.
- Hellmann M, Paz-Ares L, Caro RB, et al. Nivolumab plus Ipilimumab in Advanced Non–Small-Cell Lung Cancer. N Engl J Med. 2019; 381(21): 2020–2031.
- Reck M, Ciuleanu TE, Dols M, et al. Nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of platinum-doublet chemotherapy (chemo) vs 4 cycles chemo as first-line (1L) treatment (tx) for stage IV/recurrent non-small cell lung cancer (NSCLC): CheckMate 9LA. J Clin Oncol. 2020; 38(15_suppl): 9501–9501.
- Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021; 22(2): 198–211.
- Ramalingam S, Ciuleanu T, Pluzanski A, et al. Nivolumab + ipilimumab versus platinum-doublet chemotherapy as first-line treatment for advanced non-small cell lung cancer: Three-year update from CheckMate 227 Part 1. J Clin Oncol. 2020; 38(15_suppl): 9500–9500.
- Twomey JD, Zhang B. Cancer Immunotherapy Update: FDA-Approved Checkpoint Inhibitors and Companion Diagnostics. AAPS J. 2021; 23(2): 39.
- Vaddepally RK, Kharel P, Pandey R, et al. Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence. Cancers (Basel). 2020; 12(3).
- Rizvi NA, Cho BC, Reinmuth N, et al. MYSTIC Investigators. Durvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non-Small Cell Lung Cancer: The MYSTIC Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020; 6(5): 661–674.
- Rolfo C, Bentzen S, Devenport M, et al. First-in-human phase I/II clinical trial of ONC-392: Preserving CTLA-4 immune tolerance checkpoint for safer and more effective cancer immunotherapy. J Clin Oncol. 2020; 38(15_suppl): TPS3159–TPS3159.
- Seidel JA, Otsuka A, Kabashima K. Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations. Front Oncol. 2018; 8: 86.
- Wei SC, Anang NAAS, Sharma R, et al. Combination anti-CTLA-4 plus anti-PD-1 checkpoint blockade utilizes cellular mechanisms partially distinct from monotherapies. Proc Natl Acad Sci U S A. 2019; 116(45): 22699–22709.
- Gide TN, Quek C, Menzies AM, et al. Distinct Immune Cell Populations Define Response to Anti-PD-1 Monotherapy and Anti-PD-1/Anti-CTLA-4 Combined Therapy. Cancer Cell. 2019; 35(2): 238–255.e6.
- Park R, Lopes L, Cristancho CR, et al. Treatment-Related Adverse Events of Combination Immune Checkpoint Inhibitors: Systematic Review and Meta-Analysis. Front Oncol. 2020; 10: 258.
- Pesce S, Trabanelli S, Di Vito C, et al. Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes. Cancers (Basel). 2020; 12(12).
- Anderson AC, Joller N, Kuchroo VK. Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation. Immunity. 2016; 44(5): 989–1004.
- Solomon BL, Garrido-Laguna I. TIGIT: a novel immunotherapy target moving from bench to bedside. Cancer Immunol Immunother. 2018; 67(11): 1659–1667.
- Bendell J, Bedard P, Bang YJ, et al. Abstract CT302: Phase Ia/Ib dose-escalation study of the anti-TIGIT antibody tiragolumab as a single agent and in combination with atezolizumab in patients with advanced solid tumors. Bioinformatics, Convergence Science, and Systems Biology. 2020.
- Rodriguez-Abreu D, Johnson M, Hussein M, et al. Primary analysis of a randomized, double-blind, phase II study of the anti-TIGIT antibody tiragolumab (tira) plus atezolizumab (atezo) versus placebo plus atezo as first-line (1L) treatment in patients with PD-L1-selected NSCLC (CITYSCAPE). J Clin Oncol. 2020; 38(15_suppl): 9503–9503.
- Shan C, Li X, Zhang J. Progress of immune checkpoint LAG-3 in immunotherapy. Oncol Lett. 2020; 20(5): 207.
- Maruhashi T, Sugiura D, Okazaki IM, et al. LAG-3: from molecular functions to clinical applications. J Immunother Cancer. 2020; 8(2).
- Sanmamed MF, Pastor F, Rodriguez A, et al. Agonists of Co-stimulation in Cancer Immunotherapy Directed Against CD137, OX40, GITR, CD27, CD28, and ICOS. Semin Oncol. 2015; 42(4): 640–655.
- Starzer AM, Berghoff AS. New emerging targets in cancer immunotherapy: CD27 (TNFRSF7). ESMO Open. 2020; 4(Suppl 3): e000629.
- van de Ven K, Borst J. Targeting the T-cell co-stimulatory CD27/CD70 pathway in cancer immunotherapy: rationale and potential. Immunotherapy. 2015; 7(6): 655–667.
- Wong HYi, Schwarz H. CD137 / CD137 ligand signalling regulates the immune balance: A potential target for novel immunotherapy of autoimmune diseases. J Autoimmun. 2020; 112: 102499.
- Buchan S, Manzo T, Flutter B, et al. OX40- and CD27-mediated costimulation synergizes with anti-PD-L1 blockade by forcing exhausted CD8+ T cells to exit quiescence. J Immunol. 2015; 194(1): 125–133.
- Buchan SL, Fallatah M, Thirdborough SM, et al. PD-1 Blockade and CD27 Stimulation Activate Distinct Transcriptional Programs That Synergize for CD8 T-Cell-Driven Antitumor Immunity. Clin Cancer Res. 2018; 24(10): 2383–2394.
- Sanborn R, Pishvaian M, Callahan M, et al. Anti-CD27 agonist antibody varlilumab (varli) with nivolumab (nivo) for colorectal (CRC) and ovarian (OVA) cancer: Phase (Ph) 1/2 clinical trial results. J Clin Oncol. 2018; 36(15_suppl): 3001–3001.
- Barroso-Sousa R, Ott PA. Transformation of Old Concepts for a New Era of Cancer Immunotherapy: Cytokine Therapy and Cancer Vaccines as Combination Partners of PD1/PD-L1 Inhibitors. Curr Oncol Rep. 2018; 21(1): 1.
- Doberstein SK. Bempegaldesleukin (NKTR-214): a CD-122-biased IL-2 receptor agonist for cancer immunotherapy. Expert Opin Biol Ther. 2019; 19(12): 1223–1228.
- Khushalani NI, Diab A, Ascierto PA, et al. Bempegaldesleukin plus nivolumab in untreated, unresectable or metastatic melanoma: Phase III PIVOT IO 001 study design. Future Oncol. 2020; 16(28): 2165–2175.
- Knudson KM, Hodge JW, Schlom J, et al. Rationale for IL-15 superagonists in cancer immunotherapy. Expert Opin Biol Ther. 2020; 20(7): 705–709.
- Knudson KM, Hicks KC, Alter S, et al. Mechanisms involved in IL-15 superagonist enhancement of anti-PD-L1 therapy. J Immunother Cancer. 2019; 7(1): 82.
- Wrangle JM, Velcheti V, Patel MR, et al. ALT-803, an IL-15 superagonist, in combination with nivolumab in patients with metastatic non-small cell lung cancer: a non-randomised, open-label, phase 1b trial. Lancet Oncol. 2018; 19(5): 694–704.
- Strauss J, Heery CR, Schlom J, et al. Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, in Advanced Solid Tumors. Clin Cancer Res. 2018; 24(6): 1287–1295.
- Lee HJ. Recent Advances in the Development of TGF-β Signaling Inhibitors for Anticancer Therapy. J Cancer Prev. 2020; 25(4): 213–222.
- Ni G, Zhang Lu, Yang X, et al. Targeting interleukin-10 signalling for cancer immunotherapy, a promising and complicated task. Hum Vaccin Immunother. 2020; 16(10): 2328–2332.
- Leone RD, Emens LA. Targeting adenosine for cancer immunotherapy. J Immunother Cancer. 2018; 6(1): 57.
- Helms RS, Powell JD. Rethinking the adenosine-AR checkpoint: implications for enhancing anti-tumor immunotherapy. Curr Opin Pharmacol. 2020; 53: 77–83.
- Vigano S, Alatzoglou D, Irving M, et al. Targeting Adenosine in Cancer Immunotherapy to Enhance T-Cell Function. Front Immunol. 2019; 10: 925.
- Zhang J, Yan W, Duan W, et al. Tumor Immunotherapy Using A Adenosine Receptor Antagonists. Pharmaceuticals (Basel). 2020; 13(9).
- Cheong JE, Sun L. Targeting the IDO1/TDO2-KYN-AhR Pathway for Cancer Immunotherapy - Challenges and Opportunities. Trends Pharmacol Sci. 2018; 39(3): 307–325.
- Labadie BW, Bao R, Luke JJ. Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan-Kynurenine-Aryl Hydrocarbon Axis. Clin Cancer Res. 2019; 25(5): 1462–1471.
- Hellmann MD, Jänne PA, Opyrchal M, et al. Entinostat plus Pembrolizumab in Patients with Metastatic NSCLC Previously Treated with Anti-PD-(L)1 Therapy. Clin Cancer Res. 2021; 27(4): 1019–1028.
- Riely GJ, Ou SHI, Rybkin II, et al. KRYSTAL-1: Activity and preliminary pahrmacodynamic (PD) analysis of adagrasib (MRTX849) in patients (pts) with advanced non-small-cell lung cancer (NSCLC) harboring KRAS G12C mutation. J Thorac Oncol. 2021; 16(4S): Abstr. 990_PR.