Antitumor Activity of Synthetic Oligonucleotides with Sequences from cDNA Encoding Proteins of Mycobacterium bovis BCG

  title={Antitumor Activity of Synthetic Oligonucleotides with Sequences from cDNA Encoding Proteins of Mycobacterium bovis BCG},
  author={Tetsuro Kataoka and Saburo Yamamoto and Toshiko Yamamoto and Etsuro Kuramoto and Y Kimura and Osamu Yano and Tohru Tokunaga},
  journal={Japanese Journal of Cancer Research : Gann},
  pages={244 - 247}
Thirteen kinds of 45‐mer or 30‐mer synthetic oligonucleotides with sequences randomly selected from the cDNA encoding three kinds of protein of Mycobacterium bovis BCG were tested for their antitumor activity in a murine tumor system. Six out of the 13 single‐stranded oligonucleotides which contained one or more hexameric palindromic sequences showed strong antitumor activity while the others without palindromic structure did not. Namely, repeated intralesional injections of 100 μg of the 6… 
The discovery of immunostimulatory DNA sequence
DNA purified from BCG inhibited the growth of various animal tumors, augmented cell activity and induced IFN from mouse spleen cells, and the response of higher animals against immunostimulatory DNA must be the most primitive but important mechanism for self-nonself discrimination against foreign DNA.
Oligonucleotide Sequences Required for Natural Killer Cell Activation
The results indicated that the activity depended critically on the presence of particular palindromic sequences including the 5 ‐CG‐3 motif(s), and the size and the number of Palindromes showed the strongest activity among the oligonucleotides tested.
Activation of NK cell (human and mouse) by immunostimulatory DNA sequence
Antitumor activity of MY-1 was also abolished if the animals were pretreated with asialo GM1 antiserum or carrageenan suggesting that the activity can be ascribed mainly to activated NK cells [16].
Synthetic Oligonucleotides with Certain Palindromes Stimulate Interferon Production of Human Peripheral Blood Lymphocytes in vitro
When PBL was cultured with oligoDNA having a palindrome of AACGTT or GACGTC, IFN activity was detected by bioassay in the culture fluid after 8 h, and the amount of IFN reached the maximum after 18 h.
Hexamer palindromic oligonucleotides with 5'-CG-3' motif(s) induce production of interferon.
The results strongly suggest that the minimal essential structure required for IFN induction is the hexamer palindromic sequence with CG motif(s), and that oligonucleotides with NACGTN and NTCGAN sequences exhibited the strongest activity.
Immunomodulatory oligonucleotides as novel therapy for breast cancer: pharmacokinetics, in vitro and in vivo anticancer activity, and potentiation of antibody therapy
It is believed that the IMO is a good candidate for clinical development for breast cancer therapy used either alone or in combination with conventional cancer therapeutic agents.
DNA from Bacteria, but Not from Vertebrates, Induces Interferons, Activates Natural Killer Cells and Inhibits Tumor Growth
The nucleic acid fraction from cells of 6 species of bacterium and 2 kinds of vertebrate, calf and salmon, was extracted and purified and it was shown that the factor to activate macrophages was interferon (IFN)‐gamma and that to inhibit viral growth was IFN‐alpha/beta.
In vitro assay of immunostimulatory activities of plasmid vectors.
DNA vaccination represents a powerful new approach for the elicitation of long-lived protective immunity against a broad range of protein antigens and ultimately involves a bone marrow-derived antigen presenting cell.
Binding of oligoguanylate to scavenger receptors is required for oligonucleotides to augment NK cell activity and induce IFN.
It is suggested that the binding of an extrapalindromic sequence to the scavenger receptor is required for the immunostimulatory activity of oligo-1, a 30mer single-stranded oligonucleotide with oligoG sequences next to the active palindromo-G sequences.


Synthetic Oligonucleotides with Particular Base Sequences from the cDNA Encoding Proteins of Mycobacterium bovis BCG Induce Interferons and Activate Natural Killer Cells
It is suggested that certain palindrome sequences, like GACGTC, GGCGCC and TGCGCA, are essential for 30‐mer oligonucleotides, like BCG‐A4a, to induce IFNs.
Antitumor activity of the DNA fraction from Mycobacterium bovis BCG. II. Effects on various syngeneic mouse tumors.
MY-1 was equally effective in mice with or without presensitization with BCG, whereas BCG was much more effective in BCG-sensitized mice, suggesting that a delayed-type hypersensitivity reaction elicited by BCG protein is not required for the antitumor activity of MY-1.
Antitumor activity of deoxyribonucleic acid fraction from Mycobacterium bovis BCG. I. Isolation, physicochemical characterization, and antitumor activity.
A fraction extracted from Mycobacterium bovis strain BCG, which was composed of 70% DNA, 28.0% RNA, 1.3% protein, 0.20% glucose, and 0.1% lipid, was found to possess strong antitumor activity, suggesting that the DNA from BCG possessed strong antitUMor activity under certain conditions.
Cloning and expression of the Mycobacterium bovis BCG gene for extracellular alpha antigen
The gene for the extracellular alpha antigen of Mycobacterium bovis BCG was cloned by using a single probe restricted to G or C in the third position, and it was revealed that the alpha antigen gene encoded 323 amino acid residues, including 40 amino acids for signal peptide followed by 283 amino acids by mature protein.
Characterization, Sequence Determination, and Immunogenicity of a 64-Kilodalton Protein of Mycobacterium bovis BCG Expressed in Escherichia coli K-12
The DNA sequence of a previously cloned Mycobacterium bovis BCG gene encoding an immunogenic 64-kilodalton protein, MbaA, is reported, supporting the previously observed strong reactivity of human T-cell clones with this, for mycobacteria, common antigen.
In vivo augmentation of natural killer cell activity with a deoxyribonucleic acid fraction of BCG.
Antitumor activities of MY-1 were also abolished if the animals were pretreated with anti-asialo GM1 antiserum or carrageenan, suggesting that the activities can be ascribed mainly to activated NK cells.
Cloning of a species-specific antigen of Mycobacterium bovis
Western blots (immunoblots) showed that this cloned protein was recognized by sera from M. bovis-infected cattle, although not all cattle with bovine tuberculosis produced antibodies reactive to this clone.
In vitro Augmentation of Natural Killer Cell Activity and Production of Interferon‐α/β and ‐γ with Deoxyribonucleic Acid Fraction from Mycobacterium bovis BCG
A nucleic acid‐rich fraction extracted and purified from BCG (MY‐1) augmented natural killer (NK) cell activity of mouse spleen cells in vitro, and produced factor(s) which showed anti‐viral activity
Later phase II clinical test of MY-1 for a skin malignant tumor.
新BRM, MY-1の局所投与および皮下投与の皮膚悪性腫瘍に対する有用性を検討する目的で, 後期第II相臨床試験を実施した。局所投与の適格完全例75例の奏効率は43%であった。皮下投与においても奏効例が認められた (3/12, 25%) 。副作用はほとんどが投与部位の発赤・疼痛であった。全身性の副作用としては発熱などがあったが, 他のBRMの報告に比較すれば頻度は低く,