Journal Article
. 2019 Apr; 11(487):.
doi: 10.1126/scitranslmed.aau3259.

Targeted antibody and cytokine cancer immunotherapies through collagen affinity

Jun Ishihara 1 Ako Ishihara 1 Koichi Sasaki 1 Steve Seung-Young Lee 2 John-Michael Williford 1 Mariko Yasui 3 Hiroyuki Abe 3 Lambert Potin 1 Peyman Hosseinchi 1 Kazuto Fukunaga 1 Michal M Raczy 1 Laura T Gray 1 Aslan Mansurov 1 Kiyomitsu Katsumata 1 Masashi Fukayama 3 Stephen J Kron 2 Melody A Swartz 1 Jeffrey A Hubbell 4 
  • PMID: 30971453
  •     47 References
  •     46 citations


Cancer immunotherapy with immune checkpoint inhibitors (CPIs) and interleukin-2 (IL-2) has demonstrated clinical efficacy but is frequently accompanied with severe adverse events caused by excessive and systemic immune system activation. Here, we addressed this need by targeting both the CPI antibodies anti-cytotoxic T lymphocyte antigen 4 antibody (αCTLA4) + anti-programmed death ligand 1 antibody (αPD-L1) and the cytokine IL-2 to tumors via conjugation (for the antibodies) or recombinant fusion (for the cytokine) to a collagen-binding domain (CBD) derived from the blood protein von Willebrand factor (VWF) A3 domain, harnessing the exposure of tumor stroma collagen to blood components due to the leakiness of the tumor vasculature. We show that intravenously administered CBD protein accumulated mainly in tumors. CBD conjugation or fusion decreases the systemic toxicity of both αCTLA4 + αPD-L1 combination therapy and IL-2, for example, eliminating hepatotoxicity with the CPI molecules and ameliorating pulmonary edema with IL-2. Both CBD-CPI and CBD-IL-2 suppressed tumor growth compared to their unmodified forms in multiple murine cancer models, and both CBD-CPI and CBD-IL-2 increased tumor-infiltrating CD8+ T cells. In an orthotopic breast cancer model, combination treatment with CPI and IL-2 eradicated tumors in 9 of 13 animals with the CBD-modified drugs, whereas it did so in only 1 of 13 animals with the unmodified drugs. Thus, the A3 domain of VWF can be used to improve safety and efficacy of systemically administered tumor drugs with high translational promise.

Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.
Julie R Brahmer, Scott S Tykodi, +23 authors, Jon M Wigginton.
N Engl J Med, 2012 Jun 05; 366(26). PMID: 22658128    Free PMC article.
Highly Cited.
Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer.
S A Rosenberg, M T Lotze, +7 authors, J T Vetto.
N Engl J Med, 1985 Dec 05; 313(23). PMID: 3903508
Highly Cited.
Enhancement of the antitumor properties of interleukin-2 by its targeted delivery to the tumor blood vessel extracellular matrix.
Barbara Carnemolla, Laura Borsi, +7 authors, Luciano Zardi.
Blood, 2002 Feb 28; 99(5). PMID: 11861281
Role of IL-2 in cancer immunotherapy.
Tao Jiang, Caicun Zhou, Shengxiang Ren.
Oncoimmunology, 2016 Jul 30; 5(6). PMID: 27471638    Free PMC article.
Highly Cited. Review.
MUC1-C oncoprotein as a target in breast cancer: activation of signaling pathways and therapeutic approaches.
D W Kufe.
Oncogene, 2012 May 15; 32(9). PMID: 22580612    Free PMC article.
Highly Cited. Review.
Improving Efficacy and Safety of Agonistic Anti-CD40 Antibody Through Extracellular Matrix Affinity.
Jun Ishihara, Ako Ishihara, +6 authors, Jeffrey A Hubbell.
Mol Cancer Ther, 2018 Aug 12; 17(11). PMID: 30097487
Interleukin 2-induced increase of vascular permeability without decrease of the intravascular albumin pool.
B K Ballmer-Weber, R Dummer, +2 authors, P E Ballmer.
Br J Cancer, 1995 Jan 01; 71(1). PMID: 7819054    Free PMC article.
High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma : a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006.
Jacob A Klapper, Stephanie G Downey, +7 authors, Steven Rosenberg.
Cancer, 2008 May 07; 113(2). PMID: 18457330    Free PMC article.
Highly Cited.
Immune-Related Adverse Events Associated with Immune Checkpoint Blockade.
Michael A Postow, Robert Sidlow, Matthew D Hellmann.
N Engl J Med, 2018 Jan 11; 378(2). PMID: 29320654
Highly Cited. Review.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
Highly Cited.
Ser968Thr mutation within the A3 domain of von Willebrand factor (VWF) in two related patients leads to a defective binding of VWF to collagen.
A S Ribba, I Loisel, +5 authors, J P Girma.
Thromb Haemost, 2001 Oct 05; 86(3). PMID: 11583318
Personalized T cell-mediated cancer immunotherapy: progress and challenges.
Michael T Bethune, Alok V Joglekar.
Curr Opin Biotechnol, 2017 May 12; 48. PMID: 28494274
Multiplex three-dimensional optical mapping of tumor immune microenvironment.
Steve Seung-Young Lee, Vytautas P Bindokas, Stephen J Kron.
Sci Rep, 2017 Dec 07; 7(1). PMID: 29208908    Free PMC article.
CTLA-4 blockade in tumor models: an overview of preclinical and translational research.
Joseph F Grosso, Maria N Jure-Kunkel.
Cancer Immun, 2013 Feb 08; 13. PMID: 23390376    Free PMC article.
Highly Cited. Review.
TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells.
Sanjeev Mariathasan, Shannon J Turley, +39 authors, Thomas Powles.
Nature, 2018 Feb 15; 554(7693). PMID: 29443960    Free PMC article.
Highly Cited.
Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2.
S A Rosenberg, J C Yang, +6 authors, D E White.
JAMA, 1994 Mar 23; 271(12). PMID: 8120958
Highly Cited.
Design and Use of Chimeric Proteins Containing a Collagen-Binding Domain for Wound Healing and Bone Regeneration.
Cyril Addi, Frederic Murschel, Gregory De Crescenzo.
Tissue Eng Part B Rev, 2016 Nov 09; 23(2). PMID: 27824290
Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review.
H Maeda, J Wu, +2 authors, K Hori.
J Control Release, 2000 Mar 04; 65(1-2). PMID: 10699287
Highly Cited. Review.
Matrix-binding checkpoint immunotherapies enhance antitumor efficacy and reduce adverse events.
Jun Ishihara, Kazuto Fukunaga, +6 authors, Jeffrey A Hubbell.
Sci Transl Med, 2017 Nov 10; 9(415). PMID: 29118259
Glycoprotein VI-dependent and -independent pathways of thrombus formation in vivo.
Christophe Dubois, Laurence Panicot-Dubois, +2 authors, Barbara C Furie.
Blood, 2006 Feb 04; 107(10). PMID: 16455953    Free PMC article.
Immune checkpoint blockade: a common denominator approach to cancer therapy.
Suzanne L Topalian, Charles G Drake, Drew M Pardoll.
Cancer Cell, 2015 Apr 11; 27(4). PMID: 25858804    Free PMC article.
Highly Cited. Review.
Ado-trastuzumab Emtansine (T-DM1): an antibody-drug conjugate (ADC) for HER2-positive breast cancer.
John M Lambert, Ravi V J Chari.
J Med Chem, 2014 Jun 27; 57(16). PMID: 24967516
Highly Cited.
Improved survival with ipilimumab in patients with metastatic melanoma.
F Stephen Hodi, Steven J O'Day, +26 authors, Walter J Urba.
N Engl J Med, 2010 Jun 08; 363(8). PMID: 20525992    Free PMC article.
Highly Cited.
Why are tumour blood vessels abnormal and why is it important to know?
J A Nagy, S-H Chang, A M Dvorak, H F Dvorak.
Br J Cancer, 2009 Feb 26; 100(6). PMID: 19240721    Free PMC article.
Highly Cited. Review.
Thrombosis and von Willebrand Factor.
Minoo Shahidi.
Adv Exp Med Biol, 2016 Sep 16; 906. PMID: 27628010
Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination.
Celine Boutros, Ahmad Tarhini, +14 authors, Caroline Robert.
Nat Rev Clin Oncol, 2016 May 05; 13(8). PMID: 27141885
Highly Cited. Review.
To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery.
Fabienne Danhier, Olivier Feron, Véronique Préat.
J Control Release, 2010 Aug 28; 148(2). PMID: 20797419
Highly Cited. Review.
Reorganized Collagen in the Tumor Microenvironment of Gastric Cancer and Its Association with Prognosis.
Zhi-Hua Zhou, Cheng-Dong Ji, +3 authors, Xiu-Wu Bian.
J Cancer, 2017 Jun 24; 8(8). PMID: 28638462    Free PMC article.
PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome.
Hashem O Alsaab, Samaresh Sau, +4 authors, Arun K Iyer.
Front Pharmacol, 2017 Sep 08; 8. PMID: 28878676    Free PMC article.
Highly Cited. Review.
Synergistic innate and adaptive immune response to combination immunotherapy with anti-tumor antigen antibodies and extended serum half-life IL-2.
Eric F Zhu, Shuning A Gai, +14 authors, K Dane Wittrup.
Cancer Cell, 2015 Apr 16; 27(4). PMID: 25873172    Free PMC article.
Highly Cited.
Immune Checkpoint Blockade in Cancer Therapy: The 2015 Lasker-DeBakey Clinical Medical Research Award.
James P Allison.
JAMA, 2015 Sep 09; 314(11). PMID: 26348357
A collagen-binding EGFR antibody fragment targeting tumors with a collagen-rich extracellular matrix.
Hui Liang, Xiaoran Li, +8 authors, Jianwu Dai.
Sci Rep, 2016 Feb 18; 6. PMID: 26883295    Free PMC article.
The role of blood platelets in tumor angiogenesis.
Siamack Sabrkhany, Arjan W Griffioen, Mirjam G A Oude Egbrink.
Biochim Biophys Acta, 2010 Dec 21; 1815(2). PMID: 21167916
The collagen family.
Sylvie Ricard-Blum.
Cold Spring Harb Perspect Biol, 2011 Mar 23; 3(1). PMID: 21421911    Free PMC article.
Highly Cited. Review.
Targeting fibroblast activation protein in cancer - Prospects and caveats.
Petr Busek, Rosana Mateu, +2 authors, Aleksi Sedo.
Front Biosci (Landmark Ed), 2018 May 18; 23(10). PMID: 29772538
A collagen-binding EGFR single-chain Fv antibody fragment for the targeted cancer therapy.
Hui Liang, Xiaoran Li, +6 authors, Jianwu Dai.
J Control Release, 2015 Apr 29; 209. PMID: 25916496
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.
James Larkin, Vanna Chiarion-Sileni, +28 authors, Jedd D Wolchok.
N Engl J Med, 2015 Jun 02; 373(1). PMID: 26027431    Free PMC article.
Highly Cited.
CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells.
Sergio A Quezada, Karl S Peggs, Michael A Curran, James P Allison.
J Clin Invest, 2006 Jun 17; 116(7). PMID: 16778987    Free PMC article.
Highly Cited.
Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: A systematic analysis of the literature.
Rathi N Pillai, Madhusmita Behera, +6 authors, Suresh S Ramalingam.
Cancer, 2017 Sep 30; 124(2). PMID: 28960263    Free PMC article.
Highly Cited. Systematic Review.
Interstitial flow and its effects in soft tissues.
Melody A Swartz, Mark E Fleury.
Annu Rev Biomed Eng, 2007 Apr 27; 9. PMID: 17459001
Highly Cited. Review.
Collagen density promotes mammary tumor initiation and progression.
Paolo P Provenzano, David R Inman, +5 authors, Patricia J Keely.
BMC Med, 2008 Apr 30; 6. PMID: 18442412    Free PMC article.
Highly Cited.
Extracellular matrix proteins in hemostasis and thrombosis.
Wolfgang Bergmeier, Richard O Hynes.
Cold Spring Harb Perspect Biol, 2011 Sep 23; 4(2). PMID: 21937733    Free PMC article.
Use of radiolabelled monoclonal anti-CEA antibodies for the detection of human carcinomas by external photoscanning and tomoscintigraphy.
J P Mach, F Buchegger, +7 authors, S Carrel.
Immunol Today, 1981 Dec 01; 2(12). PMID: 25290651
Highly Cited.
The role of interleukin-2 during homeostasis and activation of the immune system.
Onur Boyman, Jonathan Sprent.
Nat Rev Immunol, 2012 Feb 22; 12(3). PMID: 22343569
Highly Cited. Review.
Circulating Cytokines Predict Immune-Related Toxicity in Melanoma Patients Receiving Anti-PD-1-Based Immunotherapy.
Su Y Lim, Jenny H Lee, +10 authors, Helen Rizos.
Clin Cancer Res, 2018 Nov 10; 25(5). PMID: 30409824
Highly Cited.
Effector CD4 and CD8 T cells and their role in the tumor microenvironment.
Sine Hadrup, Marco Donia, Per Thor Straten.
Cancer Microenviron, 2012 Dec 18; 6(2). PMID: 23242673    Free PMC article.
The future of immune checkpoint therapy.
Padmanee Sharma, James P Allison.
Science, 2015 Apr 04; 348(6230). PMID: 25838373
Highly Cited. Review.
Present Scenario of Bioconjugates in Cancer Therapy: A Review.
Aishani Wadhawan, Mary Chatterjee, Gurpal Singh.
Int J Mol Sci, 2019 Oct 28; 20(21). PMID: 31652668    Free PMC article.
Targeting inflammatory sites through collagen affinity enhances the therapeutic efficacy of anti-inflammatory antibodies.
Kiyomitsu Katsumata, Jun Ishihara, +4 authors, Jeffrey A Hubbell.
Sci Adv, 2019 Nov 15; 5(11). PMID: 31723606    Free PMC article.
Recruitment of CD103+ dendritic cells via tumor-targeted chemokine delivery enhances efficacy of checkpoint inhibitor immunotherapy.
John-Michael Williford, Jun Ishihara, +6 authors, Jeffrey A Hubbell.
Sci Adv, 2019 Dec 18; 5(12). PMID: 31844672    Free PMC article.
Engineering Targeting Materials for Therapeutic Cancer Vaccines.
Priscilla S Briquez, Sylvie Hauert, +4 authors, Jeffrey A Hubbell.
Front Bioeng Biotechnol, 2020 Mar 03; 8. PMID: 32117911    Free PMC article.
Targeted Drug Delivery via the Use of ECM-Mimetic Materials.
Jeongmin Hwang, Millicent O Sullivan, Kristi L Kiick.
Front Bioeng Biotechnol, 2020 Mar 07; 8. PMID: 32133350    Free PMC article.
Vascular modulation through exercise improves chemotherapy efficacy in Ewing sarcoma.
Miriam B G Morrell, Claudia Alvarez-Florez, +6 authors, Keri L Schadler.
Pediatr Blood Cancer, 2019 May 29; 66(9). PMID: 31136074    Free PMC article.
Engineered collagen-binding serum albumin as a drug conjugate carrier for cancer therapy.
Koichi Sasaki, Jun Ishihara, +4 authors, Jeffrey A Hubbell.
Sci Adv, 2019 Aug 28; 5(8). PMID: 31453327    Free PMC article.
Targeting Tumors Using Peptides.
Pablo Scodeller, Eliana K Asciutto.
Molecules, 2020 Feb 20; 25(4). PMID: 32069856    Free PMC article.
Tumor microenvironment complexity and therapeutic implications at a glance.
Roghayyeh Baghban, Leila Roshangar, +6 authors, Peyman Zare.
Cell Commun Signal, 2020 Apr 09; 18(1). PMID: 32264958    Free PMC article.
The role of collagen in cancer: from bench to bedside.
Shuaishuai Xu, Huaxiang Xu, +6 authors, Liang Liu.
J Transl Med, 2019 Sep 16; 17(1). PMID: 31521169    Free PMC article.
Highly Cited. Review.
Supramolecular prodrug hydrogelator as an immune booster for checkpoint blocker-based immunotherapy.
Feihu Wang, Dongqing Xu, +11 authors, Honggang Cui.
Sci Adv, 2020 Jun 04; 6(18). PMID: 32490201    Free PMC article.
Decoding the Body Language of Immunity: Tackling the Immune System at the Organism Level.
Nicolas Chevrier.
Curr Opin Syst Biol, 2020 Jun 04; 18. PMID: 32490290    Free PMC article.
Comprehensive review of targeted therapy for colorectal cancer.
Yuan-Hong Xie, Ying-Xuan Chen, Jing-Yuan Fang.
Signal Transduct Target Ther, 2020 Apr 17; 5(1). PMID: 32296018    Free PMC article.
Enhancing the Efficacy of CAR T Cells in the Tumor Microenvironment of Pancreatic Cancer.
Janina Henze, Frank Tacke, +2 authors, Wa'el Al Rawashdeh.
Cancers (Basel), 2020 Jun 03; 12(6). PMID: 32481570    Free PMC article.
Immunotherapies and Targeted Therapies in the Treatment of Metastatic Colorectal Cancer.
Prashanth Rawla, Adam Barsouk, Andreas V Hadjinicolaou, Alexander Barsouk.
Med Sci (Basel), 2019 Aug 02; 7(8). PMID: 31366129    Free PMC article.
Concepts of extracellular matrix remodelling in tumour progression and metastasis.
Juliane Winkler, Abisola Abisoye-Ogunniyan, Kevin J Metcalf, Zena Werb.
Nat Commun, 2020 Oct 11; 11(1). PMID: 33037194    Free PMC article.
Pathogen-like Nanoassemblies of Covalently Linked TLR Agonists Enhance CD8 and NK Cell-Mediated Antitumor Immunity.
Saikat Manna, Sampa Maiti, +2 authors, Aaron P Esser-Kahn.
ACS Cent Sci, 2020 Dec 05; 6(11). PMID: 33274283    Free PMC article.
Improving cancer immunotherapy using nanomedicines: progress, opportunities and challenges.
John D Martin, Horacio Cabral, Triantafyllos Stylianopoulos, Rakesh K Jain.
Nat Rev Clin Oncol, 2020 Feb 09; 17(4). PMID: 32034288    Free PMC article.
Nanomedicine for Acute Brain Injuries: Insight from Decades of Cancer Nanomedicine.
Rebecca M Kandell, Lauren E Waggoner, Ester J Kwon.
Mol Pharm, 2020 Jun 26; 18(2). PMID: 32584042    Free PMC article.
Anti-Cancer Nanomedicines: A Revolution of Tumor Immunotherapy.
Wei Li, Anghui Peng, +4 authors, Min Cui.
Front Immunol, 2021 Jan 08; 11. PMID: 33408716    Free PMC article.
Collagen-binding IL-12 enhances tumour inflammation and drives the complete remission of established immunologically cold mouse tumours.
Aslan Mansurov, Jun Ishihara, +9 authors, Jeffrey A Hubbell.
Nat Biomed Eng, 2020 Apr 15; 4(5). PMID: 32284554
Cancer immunotherapy with T-cell targeting cytokines: IL-2 and IL-7.
Ji-Hae Kim, Kun-Joo Lee, Seung-Woo Lee.
BMB Rep, 2021 Jan 08; 54(1). PMID: 33407991    Free PMC article.
CU06-1004-Induced Vascular Normalization Improves Immunotherapy by Modulating Tumor Microenvironment via Cytotoxic T Cells.
Songyi Park, Ji Hoon Oh, +8 authors, Young-Guen Kwon.
Front Immunol, 2021 Feb 16; 11. PMID: 33584714    Free PMC article.
Immunomodulating nano-adaptors potentiate antibody-based cancer immunotherapy.
Cheng-Tao Jiang, Kai-Ge Chen, +11 authors, Jun Wang.
Nat Commun, 2021 Mar 03; 12(1). PMID: 33649336    Free PMC article.
Leveraging microenvironmental synthetic lethalities to treat cancer.
Kevin J Metcalf, Alaa Alazzeh, Zena Werb, Valerie M Weaver.
J Clin Invest, 2021 Mar 16; 131(6). PMID: 33720045    Free PMC article.
Synthetic Tuning of Domain Stoichiometry in Nanobody-Enzyme Megamolecules.
Kevin J Metcalf, Blaise R Kimmel, +7 authors, Milan Mrksich.
Bioconjug Chem, 2020 Dec 11; 32(1). PMID: 33301672    Free PMC article.
A Review on Cancer Immunotherapy and Applications of Nanotechnology to Chemoimmunotherapy of Different Cancers.
Safiye Akkın, Gamze Varan, Erem Bilensoy.
Molecules, 2021 Jul 03; 26(11). PMID: 34205019    Free PMC article.
Harnessing molecular recognition for localized drug delivery.
Renjie Liu, Ran Zuo, Gregory A Hudalla.
Adv Drug Deliv Rev, 2021 Jan 24; 170. PMID: 33484737    Free PMC article.
Implantable optical fibers for immunotherapeutics delivery and tumor impedance measurement.
Ai Lin Chin, Shan Jiang, +4 authors, Rong Tong.
Nat Commun, 2021 Aug 28; 12(1). PMID: 34446702    Free PMC article.
Switchable immune modulator for tumor-specific activation of anticancer immunity.
Yu Zhao, Yu-Qing Xie, +4 authors, Li Tang.
Sci Adv, 2021 Sep 14; 7(37). PMID: 34516776    Free PMC article.
Optical Control of Cytokine Signaling via Bioinspired, Polymer-Induced Latency.
Lacey A Perdue, Priscilla Do, +8 authors, Erik C Dreaden.
Biomacromolecules, 2020 May 07; 21(7). PMID: 32374589    Free PMC article.
Tumor-Associated Extracellular Matrix: How to Be a Potential Aide to Anti-tumor Immunotherapy?
Yingying He, Tao Liu, +3 authors, Feng Luo.
Front Cell Dev Biol, 2021 Nov 05; 9. PMID: 34733848    Free PMC article.
Engineering Strategies for Immunomodulatory Cytokine Therapies - Challenges and Clinical Progress.
Ivan S Pires, Paula T Hammond, Darrell J Irvine.
Adv Ther (Weinh), 2021 Nov 05; 4(8). PMID: 34734110    Free PMC article.
Immune Modulatory Properties of Collagen in Cancer.
Anne Mette Askehøj Rømer, Marie-Louise Thorseth, Daniel Hargbøl Madsen.
Front Immunol, 2021 Dec 28; 12. PMID: 34956223    Free PMC article.
Targeting the Extracellular Matrix in Traumatic Brain Injury Increases Signal Generation from an Activity-Based Nanosensor.
Rebecca M Kandell, Julia A Kudryashev, Ester J Kwon.
ACS Nano, 2021 Dec 07; 15(12). PMID: 34870408    Free PMC article.
Maximizing response to intratumoral immunotherapy in mice by tuning local retention.
Noor Momin, Joseph R Palmeri, +8 authors, K Dane Wittrup.
Nat Commun, 2022 Jan 12; 13(1). PMID: 35013154    Free PMC article.
Protease-controlled secretion and display of intercellular signals.
Alexander E Vlahos, Jeewoo Kang, +4 authors, Xiaojing J Gao.
Nat Commun, 2022 Feb 19; 13(1). PMID: 35177637    Free PMC article.
Fibrotic activity quantified in serum by measurements of type III collagen pro-peptides can be used for prognosis across different solid tumor types.
Nicholas Willumsen, Christina Jensen, +22 authors, Morten A Karsdal.
Cell Mol Life Sci, 2022 Mar 26; 79(4). PMID: 35332383    Free PMC article.
The Intriguing Connections between von Willebrand Factor, ADAMTS13 and Cancer.
Chanukya K Colonne, Emmanuel J Favaloro, Leonardo Pasalic.
Healthcare (Basel), 2022 Mar 26; 10(3). PMID: 35327035    Free PMC article.
Reprogramming the tumor microenvironment by genome editing for precision cancer therapy.
Ke Liu, Jia-Jia Cui, +5 authors, Ji-Ye Yin.
Mol Cancer, 2022 Apr 13; 21(1). PMID: 35410257    Free PMC article.
A SIRPαFc Fusion Protein Conjugated With the Collagen-Binding Domain for Targeted Immunotherapy of Non-Small Cell Lung Cancer.
Jiayang Liu, Zhefeng Meng, +12 authors, Li Ye.
Front Immunol, 2022 Apr 16; 13. PMID: 35422796    Free PMC article.
Hydroxyethyl starch based smart nanomedicine.
Huimin Wang, Hang Hu, Hai Yang, Zifu Li.
RSC Adv, 2021 Jan 14; 11(6). PMID: 35424303    Free PMC article.
Monitoring and modulation of the tumor microenvironment for enhanced cancer modeling.
Tristen Head, Nathaniel C Cady.
Exp Biol Med (Maywood), 2022 Jan 29; 247(7). PMID: 35088603    Free PMC article.
Improving cancer immunotherapy through nanotechnology.
Michael S Goldberg.
Nat Rev Cancer, 2019 Sep 08; 19(10). PMID: 31492927
Highly Cited. Review.
Masking the immunotoxicity of interleukin-12 by fusing it with a domain of its receptor via a tumour-protease-cleavable linker.
Aslan Mansurov, Peyman Hosseinchi, +14 authors, Jeffrey A Hubbell.
Nat Biomed Eng, 2022 May 10;. PMID: 35534574